Module 4 T-cell Receptor Structure and Antigen Recognition

Question 1

T-cell receptor structure

Answer 1

Consists two polypeptide chains:

TCRα Chain TCRβ Chain

Characteristics:
1. Always membrane-bound.
2. Need somatic recombination to form a functional gene just as B cells.
3. Only recognize short peptide antigen that are derived by degradation of a pathogen’s proteins (different from the antibodies)
4. Has only one antigen binding site.

Question 2

What generates T cell receptor diversity?

Answer 2

1. Gene rearrangement / somatic recombination.
2. Junctional diversity.

Question 3

Somatic recombination and Junctional Diversity in T cells

Answer 3

The mechanisms that generate the diversity prior to antigen stimulation, are essentially the same as those operating in B cells

Question 4

T cell receptor complex

Answer 4

1. Expression of the T cell receptor on the T cell surface requires association with additional proteins
2. Before leaving the endoplasmic reticulum, the αβ heterodimer must associated with 4 invariant membrane proteins (CD3 complex + ζ chain)
3. CD3 complex is the hallmark of T cells

Question 5

Two classed of T-cell receptor

Answer 5

Mainly αβ T-cells
γδ T-cells are a small portion

Question 6

What are the differences in antigen recognition between T and B cell receptors?

Answer 6

1. TCR focuses on just proteins
2. Ignores the three-dimensional structure of proteins and concentrates instead on small linear elements of primary structure
3. It requires MHC presentation

Question 7

Types of T cell co receptors

Answer 7

CD4: T helper cells

CD8: Cytotoxic T cells

They are called co receptors because they and TCR both binds MHCs

Question 8

Types and structures of MHC molecules

Answer 8

MHC class I: present the antigens of intracellular pathogens (expressed by all nucleated cells) — CD8 T cells

MHC class II: present the antigens of extracellular pathogens (expressed mainly by professional antigen presenting cells) — CD4 T cells

Question 9

The differences between MHC class I and class II in processing of antigens for presentation?

Answer 9

See pic

Question 10

TAP

Answer 10

Transporter associated with antigen processing

Question 11

ERAP

Answer 11

Like other components of a MHC class I pathway of antigen presentation, ERAP expression is induced by interferon gamma.

Question 12

Structure of the peptide-loading complex and the process of peptide-loading to MHC class I

Answer 12

See pic

Tapasin function: The affinity of tapasin for MHC class I sets the bar that a peptide’s affinity must exceed before it can be loaded by MHC class I. This function of tapasin, in which one peptide is selected from many that were tested, is called “peptide editing”.

Question 13

Peptide loading and processing of MHC class II

Answer 13

Invariant chain prevents MHC class II from binding peptides in the ER

DM / DO balance act: DO is antagonist of DM and impedes antigen presentation by MHC

The balance between DM and DO is controlled by interferon gamma, which increases the production of DM but not DO

Question 14

MHC / HLA polymorphisms

Answer 14

Gene families: Multiple MHC class I and class II genes that are variations on a theme

Isotypes: the protein products of the different members of a MHC class I or class II gene family are called Isotypes

Isoform: the diversity arises from the combination of multiple isotypes and allotypes