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33 Cards in this Set
- Front
- Back
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What does self-MHC restriction refer to, why is it significant?
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Refers to the fact that T cells are only activated by antigens bound to self-MHC.
This contrasts B cells, which can bind any antigen floating around. |
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What is the first step in activating T cells?
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PROCESSING antigen and presenting on self-mhc.
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2 Principles of Antigen processing/presentation:
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1. the Ag must be degraded into little pieces to fit the MHC cleft.
2. The Ag must meet the MHC molecule in order to be presented. |
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Before they present, MHC molecules are found where in the cell?
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-Rough endoplasmic reticulum and Golgi complex.
Because both are proteins made like any other protein in a cell. |
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What is processed by the endogenous pathway?
What Class of MHC are these restricted to? |
Proteins generated from inside the cell.
-Viruses -Self proteins -Tumor proteins Restricted to MHC1 |
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What molecules are involved in the cytosolic (endogenous) pathway?
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-Ubiquitin
-ATP -Proteosome |
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What is Ubiquitin for?
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A signal; it binds antigens and signals the proteosome to degrade it.
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What happens to degraded proteins in the cytosol?
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-transport to RER - that's where MHC proteins are.
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What transports antigenic fragments to the RER after degradation by proteosomes?
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TAP
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What is the structure of TAP;
What does it prefer to bind? |
a heterodimer -> TAP 1 and 2.
antigens of 8 to 13 amino acids, with hydrophobic ends. |
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Without ____ and _____ MHC class 1 will not reach the membrane.
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Peptides 8-13 aa.
beta-microglobulin |
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Which class of MHC is the exogenous pathway restricted to?
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MHC2
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What antigens are presented by Class 2 MHC, and which pathway are they presented via?
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Exogenous pathway --> antigens not produced from within the cell.
-Proteins that were ingested - phagocytosed or by receptor-mediated endocytosis (bcells_ - to be presented by APCs to Thelper cells |
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steps in the endocytic, exogenous pathway:
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1. Eat antigen (with receptor or phagocyt)
2. Endosome fuses with lysosome. 3. Enzymes in lysosome hydrolyze enzyme. |
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Mechanisms to inhibit pathways
-Endogenous -Exogenous |
Endogenous: inhibit protein synthesis, inhibit production of b-microglobulin
Exogenous: give drugs to increase pH of lysosomes - won't degrade antigen. |
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What special molecule transports MHC2 out of golgi to meet antigen fragments?
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Invariant chain.
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What does invariant chain bind?
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-antigen binding cleft of MHC
-most is degraded after MHC gets out of golgi body, but a CLIP is left. |
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What must happen before Ag can bind MHC2?
What HELPS this process? |
-MHC must be taken out of golgi by invariant chain.
-CLIP must be taken out of Ag-binding cleft Nonclassical class 2 MHC |
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What two nonclassical MHCs are involved in CLIP removal?
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HLA-DM and HLA-DO.
HLA-DO --> DO remove clip HLA-DM --> prevent removal |
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What are lipid Ags presented by?
By what process? |
CD1: a nonclassical class 1 MHC
Via the exogenous pathway. |
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What does MHC present to?
MHC1: MHC2: |
MHC1 presents Antigen to Tc cells.
MHC2 presents Antigen to Th cells |
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What is the major Ag between histoincompatible individuals of same species? Why? When does it react?
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MHC; because it's polymorphic. In an allograft.
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Structure of MHC1: what two proteins, how are they arranged?
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a chain (a1, a2, a3 domains)
b-microbulin -- necessary for expression on cell surface!! |
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What is the role of B-microglobulin?
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Supporter of the alpha protein.
Not involved in anything really, just there. |
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What is the structure of MHC2, how is it arranged?
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alpha chain (a1, a2) Beta chain (B1/B2).
a1/b1 are the cleft a2/b2 are Ig domains |
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Class 1 and 2 MHC have similar binding clefts; 3 ways they are different?
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1. Cleft
2. Ag they bind 3. What they recognize |
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Difference in class 1/2 MHC clefts:
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1 - closed end
2 - open end |
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What do the clefts bind?
-MHC1 -MHC2 |
MHC1 binds Ag with 8-10 aa.
MHC2 binds Ag wtih 13-18 aa. |
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chemically, what kinds of Ag's bind
-Class 1 MHC cleft -Class 2 MHC cleft |
1: conserved en dresidues deep in the cleft.
2. Motifs at a constant elevation. |
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2 Genetic characteristics that make MHC able to bind many different Ag's;
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1. Polygenic - each person has Multiple genes encoding MHC molecules.
They DON'T REARRANGE. 2. Polymorphic - within ONE species, alleles for MHC vary btwn individuals. |
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Where is the most polymorphic variation of MHC seen?
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At the binding clefts
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What is MHC's role in susceptibility to disease?
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Your amount of less-effective MHC compared to that in the population makes a difference.
If you have MORE ineffective MHC than others, you're at a higher risk of contracting the disease of the Ag that would bind that MHC. |
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What are good and bad relative risk values?
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1 implies no higher risk
Anything greater than one implies increased risk to develop the disease. |
