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154 Cards in this Set
- Front
- Back
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The antigen receptor on T cells is called the?
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TCR
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what is necessary for a T cell to recognize a peptide to which it has a receptor?
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MHC molecules
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what does MHC stand for?
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major histocompatibility complex
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how many antigen binding sites are there on a TCR?
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1
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describe the prevelance of somatic hypermutation in T cells?
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there is none
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what are the two components of the TCR?
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the TCRalpha and the TCRbeta chains
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the heavy chain of immunoglobulins is most analagous to which TCR chain?
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the beta chain
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how many extracellular domains are there in the TCR?
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4
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does the TCR more closely relate to a FAB or FC region of the BCR?
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the FAB region
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what are the loops of hypervariability which point away from the T cell body in TCRs?
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complementary determining regions
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what is the significance of complementary determining regions?
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they are the sites at which the antigen binds
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how many loops do the alhpa and beta chains each have?
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3
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how many binding sites for antigen do immunglobulins pocess?
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2 or more
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the human T cell alpha locus is on what chromosome?
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14
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the human T cell beta locus is on what chromosome?
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7
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what is different between the constant regions of immunoglobulins as compared to that of T cells?
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T cell alpha chains only have one constant region and T cell beta chains only have one constant region whereas the B cells have multiple constant regions
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describe the gene segments of the alpha chain?
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V and J segments only just like light chains of B cells
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describe the gene segments of the beta chain?
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V, J, and D segments just like the heavy chains of B cells
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how are the V and J segments of the alpha chain joined together?
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somatic recombination
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describe the somatic recombination of the variable region of the beta chain?
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first D and J regions are joined the the V region is joined to the DJ region
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what flanks the TCR gene segements?
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recombination signal sequences
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what do the recombination signal sequences flanking TCR gene segment encode for?
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RAG1 and RAG2
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what process adds aditional diversity during recombination?
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addition of N and P nucleotides in the junctions between gene segments
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what disorder is the result of nonfunctional RAG genes?
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severe combined immunodificiency disease (SCIDs)
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why is SCIDs called a combined disorder?
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both T and B cells are equally absent
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what is the treatment for SCIDs?
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bone marrow transplant
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what is the disorder that results from misense mutations in RAG genes leaving only partial enzymatic activty?
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Omenn Syndrome
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where are the alpha and beta chains paired to form the alpha/beta receptor?
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the ER
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what are the 2 invarent proteins which alpha/beta chains must associate with to form the TCR?
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1. CD3 complex - chromosome 11
2. xeta chain - chromosome 1 |
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after an antigen has been recognized by alpha/beta chains what transmits this signal to the interior of the T cell?
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CD3 complex and zeta chain
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what is the other TCR besides the alpha/beta receptor?
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the gamma/delta receptor
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where is the delta chain gene locus?
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inside the alpha chain gene locus on chromosome 14 between the V and J segments
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what is the consequence for rearrangement of the alpha chain mean for the delta gene locus?
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it is cut out of chromsome 14 and thus nonfunctional
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which chromosome does the gamma chain gene locus belong on?
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chromosome 7
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which has more variable region, alpha/beta or gamma/delta TCRs?
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alpha/beta
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how is more diversity achieved with the delta chain?
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it contains two diversity segments instead of the normal 1
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what are the two ways having two D segments increases the diversity of the gamma/delta TCR?
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1. allows for more combinations of gene segments
2. allows for an extra joining region for the insertion of N and P nucleotides |
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what is the maximal percentage of T cells expressing gamma/delta receptors in each individal?
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5%
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where are gamma/delta T cells considered to be the majority in the body?
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in epithelial tissue
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what major restriction are gamma/delta T cells free from that is associated with T cells?
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they do not have to have the help of MCH molecules to recognize antigens
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what is the term that refers to the degredation and recognition of a protein antigen
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antigen processing
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the binding of a peptide antigen by an MCH molecule and its display on the cell surface is called?
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antigen presenting
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what are the two types of alpha/beta T cells
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CD4 and CD8
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CD4 and CD8 are considered to be which type of molecules?
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glycoprotiens
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which alpha/beta T cells are designed to kill cells that are infected by an intracellular pathogen?
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CD8 T cells a.k.a. cytotoxic T cells
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which type of alpha/beta T cells are designes to respond to extracellular sources of infection?
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CD4 T cells a.k.a. helper T cells
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TH2 cells are mainly involved with what function?
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helping B cells produce antibodies to extracellular bacteria and virus particles
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what is the function of TH1 cells?
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activate tissue macrophages to phagocytize and kill extracellular pathogens and release cytkines and other biologically active compounds
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AIDS selectively affects which type of T cells?
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TH1 T cells a.k.a. CD4 T cells
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how does the HIVE virus gain access to CD4 T cells?
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via the CD4 receptor
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what are the two different types of MHC molecules?
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Class I and II
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which MHC molecule presents antigens of intracellular origin?
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MCH class I
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which MHC molecule presents antigens of extracellular origin?
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MHC class II
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what is another name for CD4 and CD8 molecules?
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T cell co-receptors
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describe the MHC class I receptor?
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a transmembrane heavy chain made up of 3 extracellular domains (alpha 1, 2, and 3) complexed with the protein Beta2-microglobulin
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what forms the antigen binding-site of the MCH class I molecule?
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alpha 1 and 2 extracellular domains
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what supports the antigen binding site in MHC class I molecules?
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the alpha 3 extracellular domain and Beta2-microglobulin
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describe the structure of the MHC class II molecule?
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a beta and alpha chain each consisting of two extracellular domains
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describe the antigen binding site structure in MHC class II molecules?
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composed of Beta-1 and Alpha-1 extracellular domains
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what supports the antigen binding site in MHC class II molecules?
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Beta-2 and Alpha-2
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what are the molecules which bind to the supporting, immunoglobulin like bases of the MHC molecules?
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CD4 and CD8
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compared to the highly specific binding of TCRs or immunoglobulins, MHC specificity is described by what term?
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degenerative binding specificity (binds many different antigens)
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what determines the type of antigen that a MHC molecule can bind and causes the differences between the binding of MHC class I and class II?
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the size of the binding groove
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which MCH molecule can bind longer more variable peptides?
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MCH class II (13-25 AA long)
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where are peptides derived from intracellular pathogens formed?
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the cytosol
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where do MCH class I molecules bind pepetides from the cytosol?
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in the ER
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where are extracellular pathogens broken down into peptides?
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in endocytic vesicles like lysosomes
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where do MCH class II molecules bind to extracellular pathogen peptides?
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inside endocytic vesicles
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proteins in the cytosol are degraded by what?
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the proteasome
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what transports peptides from intracellular pathogens into the ER?
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transporter associated with antigen processing (TAP)
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what type of transport is provided by TAP?
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Active (ATP dependent)
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what helps to complete the folding and peptide binding of MHC molecules?
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chaperone protiens
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what do MHC heavy chains first bind when they enter the ER?
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the membrane protein calnexin
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what is the function of calnexin?
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to maintain the partially folded MCH heavy chains while in the ER
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what is calnexin dependent on to function?
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calcium
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after the MHC heavy chain binds Beta2-microglobulin, calnexin is released and is replaced by chaperone-like protein?
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calreticulin
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what else binds alongside calreticulin?
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tapasin
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what is the function of tapasin?
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to bind TAP1 and position the MCH molecule to recieve a peptide antigen
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after binding antigen what happens to the MHc I molecule?
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it releases its chaperones and moves to the cell surface
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what is the cause of MCH I loss on cell surfaces in bare lymphocyte syndrome?
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TAP protein is deficient and cannot transport peptides into the ER
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where are extracellular pathogens stored once they have been endocytized or phagocytized?
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in endocytic vesicles or phagozomes
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what do the vesicles formed by the intake of extracellular pathogens fuse with?
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lysosomes and other digestive enzyme vesicles
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after degredation and binding of peptide to MHC class II molecules in the vesicular pathway, what happends to the MHC molecules?
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they are brought to the surface of the cell in vesicles and expressed on the cell surface
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what is the third chain that the alpha and beta chains of the MCH calss II bind with?
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the invariant chain
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how does the invariant chain work?
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it block the peptide binding site of MCH II molecules while in the ER so only MCH I molecules bind the peptide found there
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besides its function in the ER what else does the invariant chain do for MCH II molecules?
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it directs them to the vesicles which will meet up with the endocytic vesicles and phagozomes
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what are the vesicles which transport MCH II to the vesicular pathway?
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MIICs or MHC class II compartments
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what happens to the invariant chain in the MIIC?
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it is degraded by proteases
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what is left of the invariant chain after protease activity in the MIICs?
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just the small peptide which covers the binding site of the MCH II molecule
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what is the name of the small peptide which covers the binding site of the MCH II molecule
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class II-associated invariant-chain peptide (CLIP)
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what helps to remove CLIP from the binding site of the MCH II molecule once it has reached its destination?
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HLA-DM
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what makes each MHC molecules specific for its associated T cell?
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the T cell not only binds the presented peptide, but also attaches to the surface of the MCH molecule
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which CDR loop(s) form the central binding site in TCRs?
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CDR3
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which CDR loops in the TCR form the periphery binding site for the MCH molecule?
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CDR1 and CDR2
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which CDR loop in the TCR directly contacts the peptide presented by the MCH molecule?
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CDR3
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which TCR chain makes a stronger contact with the presented peptide/MCH complex?
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the alpha chain CDR1 and CDR2
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which CDR loop is the most variable?
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the CDR3 loop becuase it contains all the variant, joining, and (for the beta chains) the diversity segments
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which MCH class is expressed in all cells?
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MCH I
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what is the only cell in the body that does not express MCH I?
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the RBC -> might be why they are continuously infected by malaria
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which cell types express MCH II molecules?
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the cells of the immune system specialized in uptake, processing, and presentation of antigens from the external environment
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what are the 3 professional antigen-presenting cells?
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1. dendritic cells
2. macrophages 3. B cells |
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what is the function of INF-gamma?
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upregulation of MHC I and II molecule production and expression
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where are the genes for MHC molecules and other protiens for antigen processing and presentation located?
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on chromosome 6
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what is the region on chromosome 6 called which encodes genes for MHC molecules and other proteins for antigen processing and presentation?
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major histocompatibility complex
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what is the human MHC called?
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the "human leukocyte antigen (HLA) complex"
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different forms of a given gene are called?
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alleles
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different forms of a gene give rise to different forms of a protein which are called?
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allotypes
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a molecule that arises from multiple families of genes and their proteins is called?
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a isoform
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the different MHC molecules are called ___ of each other?
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isoforms
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describe the degree of polymorphism in the alleles coding for MHC molecules as compared to other polymorphic genes in the body?
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MHC are considered highly porlymorphic (multiple different genes which all encode MCH molecules)
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some MHC genes have only one allele and these are called?
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monomorphic
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some MHC gene have only a few alleles and these are called?
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oligomorphic
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what are the 6 MHC class I isotypes?
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1. HLA-A
2. HLA-B 3. HLA-C 4. HLA-E 5. HLA-F 6. HLA-G |
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what are the 5 MHC class II isotypes?
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1. HLA-DM
2. HLA-DO 3. HLA-DP 4. HLA-DQ 5. HLA-DR |
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which of the class I isotypes are higly polymorphic? (3)
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1. HLA-A
2. HLA-B 3. HLA-C |
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what is the function of the highly polymorphic class I isotypes?
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present antigens to CD8 T cells and form ligands for receptors on NK cells
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which of the class I isotypes is considered oligomorphic? (2)
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1. HLA-E
2. HLA-G |
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what is the function of the oligomorphic class I isotypes?
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form ligand for NK cells
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what is the monomorphic class I isotype?
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HLA-F
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what is the function of HLA-F?
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unknown
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which class II isotypes are considered highly polymorphic? (3)
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1. HLA-DP
2. HLA-DQ 3. HLA-DR |
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what is the function of the highly polymorphic class II isotypes?
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present peptide antigen directly to CD4 T cells
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describe the genetic polymorphism of HLA-DM and HLA-DO?
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oligomorphic
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what is the function of the oligomorphic class II isotypes?
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regulate the peptide loading into the highly polymorphic class II isotypes
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which HLA MHC class has the greatest diversity?
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Class I
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describe the regions of the MHC on chromosome 6?
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at one end is the class I region and at the other is the class II region and sepperating the two is the class III region
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in what region of chromosome 6 is the invariant light chain, Beta2-microglobulin located?
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TRICK! its not on chromosome 6 where the other MCH components are found. It is instead on chromosome 15.
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for a discussion on naming HLA class II molecules look on Page 88 of Parham first paragraph
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:)
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the particular comination of HLA alleles found on a given chromosome 6 is known as the?
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halpotype
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what is the minimum number of MHC molecules a person can express?
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the can be homozygous and express only three for each class for a total of 6 isoforms
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what is the max number of MHC molecules a person can express?
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14 because the max class I is 6 and the max class II is 8
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the class II region of the MHC is mostly dedicated to genes involved in what?
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the processing of antigens and their presentation to T cells, NOT MHC genes
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in addition to HLA Class II isotypes, what other genes are contained in the class II region of chromosome 6? (3)
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1. TAP peptide tranporter
2. tapasin 3. subunits of preteosome LMP2 and LMP7 |
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what are the cytokines which regulate genes encoding proteins which work together in antigen processing and presentaiton?
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IFN-alpa, IFN-beta, and IFN-gamma
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what do these cytokines do to increase the proccessing and presentation of intracellular pathogens?
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upregulate MHC class I heavy chain (alpha chain) production, Beta2-microglobulin, TAP proteins, and LMP2 and LMP7
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expression of the class II isoforms is regulated by?
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INF-gamma
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what turns on the genes endcoding MHC class II isoforms?
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MHC class II transactivator (CIITA)
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what happens when inherited CIITA is nonfunctional or impared?
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bare lymphocyte syndrome in which CD4 T cells are nonfunctioning
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what is the sole function of MHC class II genes?
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antigen presentation
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what are some of the broad functions of MHC class I genes (3)
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1. uptake of IgG in gut
2. regulation of iron metabolism 3. regulation of NK cell function |
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where are the polymorphisms which create the differences between MHC molecules mainly found?
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in the domains that bind antigen and interact with the TCR (alpha I and II of both the MHC class I and alpha-I and beta-I of class II)
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which of the MHC class II isotypes is invariant?
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HLA-DR alpha chain
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the AA's that anchor the peptide to the MHC molecule are called?
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anchor residues
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the combination of anchor residues that binds to a particular MHC isoform is called the?
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peptide-binding motif
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where are the anchor residues found in the MHC class I molecule?
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psotions 2 and 9
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the rule that the antigen-specific T cell response is restriced by the MHC type is known as?
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MHC restriction - a T cell can only respons to one type of MHC and only one type of peptide thus both must be present for binding to happen
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what is the principle that say certain HLA allotypes are maintained in population despite the prevelance of polymorphisms becuase of their peptide-binding specificities?
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balancing selection
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under certain conditions such as epidemic disease, balancing selection is over ruled by selection for newer variants which have more potential. What is this called?
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directional selection
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what is the most favored way to create variants in HLA class I and II alleles?
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intrallelic conversion or segmental exchange (recombination of small homologous segments between alleles)
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in the context of T cell recognition self-MHC isoforms are termed?
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autologous
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in the context of T cell recognition all non-self MHC molecules are termed?
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allogenic
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T cells which recognize allogenic MHC/peptide complexes are termed?
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alloreactive
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what is the term used to describe the recognition by T cells of transplanted tissue with non-self MHC molecules?
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alloreaction
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becuase of alloreaction, what must be matched up between donor and receiver of organs?
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the HLA type
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