export_chapter 6 mhc Flashcards by Matthew Godwin

2 properties of antigens recognized by T cells

short linear peptides

* presented on MHC molecules

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MHC Restriction

T cells can only see an antigen on a SPECIFIC type of MHC molecule

T cells from a given individual only recognize antigens in the context of their own MHC

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Number of signals needed to activate a naive T cell

2 (some say 3)
1 = antigen on MHC

2 = microbial product

3 = cytokines

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Effects of interaction of a dendritic cell with a naive T cell

Naive T cell activation
clonal expansion
differentiation –> effector T cells

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Effects of macrophage interaction with T cells

Effector T cell activation

* Activation of macrophages (cell mediated immunity)

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Number of signals required to activate an effector T cell

1 - antigen on MHC

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Effects of Effector T cell interaction with B cells

Effector T cell activation
B cell activation
Antibody production (humoral immunity)

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CD40 and CD40 ligand

Receptor and ligand pair important for T and B cell interaction

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Adjuvant

Microbial products that enhance antigen presentation to make a stronger response

Often used in vaccines

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“Hole in the repertoire”

When inbred populations don’t have the MHC gene needed to present a particular antigen to get a good response

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Genetic polymorphisms

genes whose products can be different between individuals

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Alleles

Variants in polymorphic genes

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Co-dominant alleles

Both are expressed even if they are different

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Are MHC genes polymorphic or polygenic?

both

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Polygenic

Multiple genes for the same thing

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Syngeneic individuals

express the same alleles

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Allogeneic individuals

express at least one differing allele

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HLA

Human leukocyte antigen

Human MHC gene

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Names of human Class I MHC loci

A, B, C

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Names of human MHC Class II loci

DP, DQ, DR

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H-2

Mouse MHC gene

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Names of mouse MHC class I loci

D, L, K

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Names of mouse MHC class II loci

I-A (A), I-E (E)

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CLA

Canine leukocyte antigen

Canine MHC gene

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FLA

feline leukocyte antigen Feline MHC gene

Besides MHC genes, what other genes are located on MHC regions?

Cytokine genes

H-2 Kd

Mouse class 1 MHC K gene, allele d

I-Ad

Mouse Class II MHC A gene, d allele

H-2d

Genetic haplotype All genes have the d allele

HLA-B27

Human Class I MHC Gene B, allele 27

HLA-DR4

Human Class II MHC Gene DR, allele 4

MHC haplotype

The set of alleles for a given individual

MHC class I molecules - what are the 2 polypeptide chains?

alpha | beta2-microglobulin

Class II MHC polypeptide chains

a, b

Locations of polymorphic residues in Class I MHC

a1 and a2

Locations of polymorphic residues in Class II MHC

a1 and b1

Binding site for T cell receptor on Class I MHC

a3 region

Type of cell that recognizes class I MHC

CD8 T cells

Binding site for T cell on class II MHC

b2 region

Type of cell that recognizes Class II MHC

CD4 T cell

Size of peptide-binding cleft in Class I MHC

small, 8-11 residues

Size of binding site in Class II MHC

large, 10-30 residues

Types of cells expressing Class I MHC

All nucleated cells

Types of cells expressing Class II MHC

Professional APCs | B cell, dendritic cell, macrophage

What is the effect of IFN-gamma on MHC?

Increases expression of MHC on macrophages

TAP

Transporter associated protein In ER membrane Transports peptides from cytosol into ER lumen to make Class I MHC

How often is class I MHC made?

Constituitively, all the time

Steps in antigen processing for Class I MHC

1. Cytosolic/intracellularprotein cut into peptides by proteasome 2. TAP transports peptides into ER lumen 3. Peptides bind to MHC in the ER 4. MHC transported to the cell membrane

Steps in antigen processing for Class II MHC

1. extracellular protein endocytosed 2. Protein broken down in endosome 3. MHC with invariant chain transported from ER to endosomal compartment 4. invariant chain cleaved out 5. Peptide binds to MHC 6. MHC transported to cell membrane

Name the chains in Class II MHC

a and b chain

Name the chains in Class I MHC

a chain and b2 microglobulin

What cells present antigens on Class II MHC?

Dendritic cells, macrophages and B lymphocytes "Professional APCs"

What cells present antigens on class I MHC?

All nucleated cells

What type of cell responds to Class II MHC?

CD4 helper T cells

What type of cells respond to Class I MHC?

CD8 cytotoxic T cells

What is the source of protein antigen for Class II MHC?

Endosomal/lysosomal proteins internalized from the extracellular environment

What is the source of protein antigens for Class I MHC?

Cytosolic proteins synthesized in the cell

Site of peptide loading on Class II MHC

Endosome/lysosome compartment

Site of peptide loading on Class I MHC

endoplasmic reticulum

Invariant chain is involved in antigen presentation on which MHC molecule?

Class II

How are proteins labeled for degradation?

Ubiquitination

What guides class II MHC to the endocytic vesicle?

Specific AAs on invariant chain

What is the function of HLA-DM?

cleaves CLIP

What is CLIP?

part of invariant chain resistant to enzymatic degradation in the endosome removed by HLA-DM

What is an immunodominant epitope?

A peptide that activates and immune response better than other peptide antigens from the same protein

Where do proteins go after ubiquitination?

proteasome

For which type of MHC does the antigen processing involve ubiquitination?

Class I

For which type of MHC does the processing involve degradation in the proteasome?

Class I

For which type of MHC is TAP involved in antigen processing?

Class I

For which type of MHC does antigen processing involve protein degradation in the endosome/lysosome?

Class II

For which type of MHC is CLIP inolved in antigen processing/presentation?

Class II

For which type of MHC is invariant chain involved in MHC production?

Class II

What is cross-presentation?

Ability of dendritic cells to display extracellular antigen on class I MHC (which would normally go through the class II pathway) to activate naive CD8 (cytotoxic) T cells. (Dendritic cells are the only cells that can activate naive T cells)