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33 Cards in this Set

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  • Back
What does self-MHC restriction refer to, why is it significant?
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.
What is the first step in activating T cells?
PROCESSING antigen and presenting on self-mhc.
2 Principles of Antigen processing/presentation:
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.
Before they present, MHC molecules are found where in the cell?
-Rough endoplasmic reticulum and Golgi complex.

Because both are proteins made like any other protein in a cell.
What is processed by the endogenous pathway?

What Class of MHC are these restricted to?
Proteins generated from inside the cell.

-Self proteins
-Tumor proteins

Restricted to MHC1
What molecules are involved in the cytosolic (endogenous) pathway?
What is Ubiquitin for?
A signal; it binds antigens and signals the proteosome to degrade it.
What happens to degraded proteins in the cytosol?
-transport to RER - that's where MHC proteins are.
What transports antigenic fragments to the RER after degradation by proteosomes?
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.
Without ____ and _____ MHC class 1 will not reach the membrane.
Peptides 8-13 aa.

Which class of MHC is the exogenous pathway restricted to?
What antigens are presented by Class 2 MHC, and which pathway are they presented via?
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
steps in the endocytic, exogenous pathway:
1. Eat antigen (with receptor or phagocyt)
2. Endosome fuses with lysosome.
3. Enzymes in lysosome hydrolyze enzyme.
Mechanisms to inhibit pathways
Endogenous: inhibit protein synthesis, inhibit production of b-microglobulin

Exogenous: give drugs to increase pH of lysosomes - won't degrade antigen.
What special molecule transports MHC2 out of golgi to meet antigen fragments?
Invariant chain.
What does invariant chain bind?
-antigen binding cleft of MHC

-most is degraded after MHC gets out of golgi body, but a CLIP is left.
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
What two nonclassical MHCs are involved in CLIP removal?

HLA-DO --> DO remove clip

HLA-DM --> prevent removal
What are lipid Ags presented by?

By what process?
CD1: a nonclassical class 1 MHC

Via the exogenous pathway.
What does MHC present to?

MHC1 presents Antigen to Tc cells.

MHC2 presents Antigen to Th cells
What is the major Ag between histoincompatible individuals of same species? Why? When does it react?
MHC; because it's polymorphic. In an allograft.
Structure of MHC1: what two proteins, how are they arranged?
a chain (a1, a2, a3 domains)

b-microbulin -- necessary for expression on cell surface!!
What is the role of B-microglobulin?
Supporter of the alpha protein.

Not involved in anything really, just there.
What is the structure of MHC2, how is it arranged?
alpha chain (a1, a2) Beta chain (B1/B2).

a1/b1 are the cleft
a2/b2 are Ig domains
Class 1 and 2 MHC have similar binding clefts; 3 ways they are different?
1. Cleft
2. Ag they bind
3. What they recognize
Difference in class 1/2 MHC clefts:
1 - closed end

2 - open end
What do the clefts bind?
MHC1 binds Ag with 8-10 aa.

MHC2 binds Ag wtih 13-18 aa.
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.
2 Genetic characteristics that make MHC able to bind many different Ag's;
1. Polygenic - each person has Multiple genes encoding MHC molecules.

2. Polymorphic - within ONE species, alleles for MHC vary btwn individuals.
Where is the most polymorphic variation of MHC seen?
At the binding clefts
What is MHC's role in susceptibility to disease?
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.
What are good and bad relative risk values?
1 implies no higher risk

Anything greater than one implies increased risk to develop the disease.