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78 Cards in this Set
- Front
- Back
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which TCR genes are equivalent to light chains in immunoglobulins?
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alpha and gamma (VJ rearrangement)
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which TCR genes are equivalent to heavy chains in immunoglobulins?
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beta and delta (VDJ rearrangement)
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which two TCR genes are located on chromosome 14?
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alpha and delta
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what is the TCR complex composed of?
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four dimers: CD3 and TCR; CD3 is composed of 3 pairs of chains responsible for cell signaling
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is the antigen-binding interaction of T-cell receptors stronger or weaker than that of antibodies?
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TCR-Ag interaction is weaker than that of antibodies!
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the multicomponent signal-transducing CD3 molecule associated with TCR has a function analogous to what in IgM?
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the Ig-alpha/Ig-beta complex of B cell receptor
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the ab TCR is considered to be a signature molecule of the ______immune system. By contrast, the yd TCR function in a manner more consistent with ________ immunity.
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the ab TCR = adaptive (like Ab)
the yd TCR = innate (recognizes classes of antigens present on groups of pathogens) |
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what antibody could be used to isolate only T-cells?
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anti CD3
because all T-cells have CDR molecules in conjunction with their T-cell receptors |
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do TCR and Ig have common recognition elements?
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no, they are encoded by entirely separate gene families
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which experiment demonstrated self-MHC restriction of T-cell receptor?
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the mice infected with LCM produced LCM-specific CTLs that could only lyse LCM-infected target cells presented with self-MHC molecules
CTL and virus-infected target cell must share class I MHC molecules (207) |
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what two things (binding) are TCRs specific for?
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both antigen and self-MHC molecule
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what are the components of a TCR?
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variable domain, constant domain, conecting sequence, transmembrane region, cytoplasmic tail
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why are the transmembrane regions unique in TCR?
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they contain positively charged AA that promote interaction with CD3 molecule for signal transduction
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which heterodimeric TCR is found most frequently in human peripheral blood?
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(yd) gamma-delta
(in peripheral/circulating blood- more of an innate immune function: yd TCR recognizes microbial phospholipid on intact/unprocessed protein) does not need mhc! |
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the predominant receptor found of yd TCR recognizes what?
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the microbial phospholipid antigen 3-formyl-1-butyl pyrophosphate found on
mycobacterium tuberculosis and other bacteria and parasites |
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what are the four TCR loci?
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a, b, y, d
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the genes that encode the ab and yd TCR are expressed only in cells of the _____ lineage.
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T-cell!
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which TCR genes are ~ to light chain in Ig?
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alpha and gamma (y) !
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which TCR genes are ~ to heavy chain in Ig?
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beta and delta!
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what is the benefit of having ad (and by in humans) on same chromosome?
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on chromosome 14, the delta-chain gene segments are located BETWEEN Va and Ja gene segments so that during a productive alpha-chain rearrangement, Cd (delta gene-segments) are deleted so that in a given T cell, the ab TCR cannot be coexpressed with the yd receptor
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does somatic hypermutation occur in TCR gene rearrangement?
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nope
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where does alternative joining of D gene segments come into play it TCR gene rearrangement?
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in beta and delta chain rearrangement (VDJ) can have D-D joining due to positioning of RSS's providing more combinations that Ig
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what are the two examples of allelic exclusion in TCR gene rearrangement?
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1. having a/d gene-segments on same chromosome (deletion of d)
2. duplicated J and C gene-segments on chromosome coding for the b-chain. |
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are alpha or beta chain genes more subject to allelic exclusion?
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beta!
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combinatorial joining of ab V gene segments generates ____ and _____, whereas junctional flexibility and N-region nucleotide addition generate ______.
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combinatorial joining = CDR1 & CDR2
junctional flex and N-addition = CDR3 |
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in the interaction between ab TCRs and antigen, what provides the primary contact with the antigenic peptide presented by MHC molecules?
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CDR3
Note difference between CDR3 and CD3 ***** |
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what is required for expression of TCR on T-cell membrane?
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expression of CD3
loss of genes encoding either CD3 or TCR chains results in absence of entire complex from T cell surface |
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what is true about the transmembrane region on all the CD3 polypeptide chains?
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they contain negatively charged AA residues (aspartic or glutamic acid) that interact with with the positively charged AA's in the transmembrane region of each TCR chain
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what is ITAM? function?
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"immunoreceptor tyrosine-based activation motif"
the motif found in the cytoplasmic tails of the CD3 chains interact with tyrosine kinase play important role in signal transduction |
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what are the five invariant polypeptide chains of the CD3?
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y, d, e, z, n
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CD3 is a complex of 5 what?
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invariant polypeptide chains that associate to form 3 dimers
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how many ITAMs do each of the CD3 chains have?
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y, d, e: 1 each
z, n: 3 each |
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how is the interaction between the TCR complex and the CD4 molecule stabilized?
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the signal transduction molecule p56lck interacts dually with CD4 and the zz homodimer of the CD3 complex
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what is P56lck?
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a signal transduction molecule that interacts with the zz homodimer of the CD3 complex and CD4 to stabilize CD4-MHC interaction, thus stabilizing the interaction between Tcell and APC
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what does allogenic mean?
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genetically different member of same species
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what is an allograft?
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graft from same species
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what is direct allorecognition?
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T cell recognizes foreign MHC because it is similar to own
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what is indirect allorecognition?
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T cells recognize foreign MHC after it is processed and presented on self-MHC (like any other antigen)
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what is a thymocyte?
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developing T cell in the thymus
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what is positive selection?
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permits the survival of only those T cells whose TCRs are capable of recognizing self-MHC molecules
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which type of Tcell selection is responsible for the creation of a self-MHC-restricted repertoire of T cells?
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positive selection
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what is negative selection?
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eliminates T cells that react too strongly with self MHC or with self MHC + self peptide
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which type of T cell selection is extremely important in generating T cells that are self-tolerant?
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negative selection
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what is the purpose of the period of rapid proliferation in the DP stage prior to alpha -chain rearrangement?
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increase diversity ...p248
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what two things must happen in the double positive phase to trigger alpha-chain rearrangement?
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1. double positive thymocytes stop proliferating
2. RAG-2 protein levels increase |
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where does positive selection take place?
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cortical region of thymus
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which occurs first, positive or negative selection?
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positive
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what is TAP1?
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a peptide transporter required for normal expression of MHC I and development of CD8+ thymocytes
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what is the avidity hypothesis?
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differences is strength of signals received by thymocytes undergoing positive and negative determine the outcome
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what is the differential-signaling hypothesis?
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different signals altogether (not varying signal strength) are responsible for the outcome of thymocytes undergoing positive and negative selection
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the avidity hypothesis and differential-signalling hypothesis account for what?
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the fine line that is the paradox in pos/neg selection -the signals make the difference!
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a decrease in peptide favors which selection
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positive -(not much binding)
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an increase in peptide favors which selection?
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negative -(lots of binding)
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a partial peptide signal favors which selection?
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positive
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a complete peptide signal favors which selection?
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negative
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what are the two models proposed to explain the transformation of a double positive precursor into one of the two different single-positve lineages?
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1. instructive model -multiple interactions between the TCR, CD8 or CD4 and class I or II MHC instruct cells
2. stochastic model - random-no relation to specificity of TCR |
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T-cell activation ultimately leads to what?
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gene activation
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what are the two phases of antigen-mediated induction of T-cell response?
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initiation and signal generation
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what is an immunological synapse?
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a feature of the initiation phase of TCR signaling -a supramolecular structure
critical feature of IS formation is entry of TCR into lipid raft |
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what 2 signals (co-stimulation) are required for T-cell activation
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1. interaction with CD3/TCR and proper antigen
2. (costimulation) of CD28 molecule on Tcell by B7 on APC (not Ag specific) |
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what are the ligands for B7 (APC) on T-cell?
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CD28 and CTLA-4
CD28 activates T-cell CTLA-4 inhibits activation |
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expression of IL-2 related genes requires what?
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CD28 (on Tcell) activation by b7
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what do superantigens bind to?
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the variable beta domain of TCR and alpha domain of MHCII (but not via binding sites!!)
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how can superantigens influence T-cell maturation in the thymus?
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a superantigen present in the thymus induces negative selection of all thymocytes bearing a TCR variable b domain recognized by superantigen --> massive deletion characterized by absence of Tcells whose receptors poses vb domains recognized by the superantigen
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what is the difference between endogenous and exogenous superantigens?
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exogenous- soluble protein secreted by bacteria
endogenous- membrane bound protein encoded by certain viruses |
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which is the best professional APC? why?
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dendritic cells because they always express high levels of class I and II MHC molecules as well as high levels of B71 and 2, while all other professional APCs require activation for expression of B7 molecules
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what are cytokines?
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low mw proteins of glycoproteins
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how do cytokines regulate the intensity/duration of an immune response?
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by stimulating or inhibiting the activation, proliferation and differentiation of various cells and by regulating the secretion of antibodies or other cytokines
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what are the attributes exhibited by cytokines?
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pleiotropy, redundancy, syngery, antagonism, cascade induction
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what are the four classes of cytokines?
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hematopoetin
interferon chemokine TNF |
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what are the main producers of cytokines?
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helper T cells, macrophages and dendritic cells
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how is specificity of the immune system maintained with cytokines acting in an antigen-nonspecific manner?
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1. regulation of expression of cytokine receptors -often only expressed after cell has interacted with an Ag
2. regulation of secretion of cytokines -must be interacting directly with target cell 3. half life of cytokines is very short to ensure that they act for a short time over short distance |
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what explains redundancy/antagonism exhibited by some cytokines?
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sharing of signal-transducing subunits among receptors
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what does the presence of high levels of CD25 in mature T cells suggest?
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that cells are in a state of activation and/or that cells of the Treg subset (CD4+ +CD25!)
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which type of receptor is associated with a G protein?
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chemokine
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in which two classes of cytokine receptors do the majority of receptors fall?
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class I and II (hematopoetin and interferon)
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do class I and II receptors have signalling motifs (such as intrinsic tyrosine kinase domains) ?
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no!
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what is IL-1Ra?
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an IL-1 receptor antagonist responsible for mediating intensity of inflammatory response
potential treatment for chronic inflammatory disease |
