017 Antigen recognition: T-cells and MHC

Question 1

Where do T-cells mature?

Answer 1

Thymus

Question 2

Which type of T-cells generate immunity to viruses?

Answer 2

CD8+

Question 3

Which type of T-cells generate immmunity to intracellular bugs?

Answer 3

cd4+

Question 4

What is the structure of the TCR receptor?

Answer 4

Heterozygous dimer with either alpha/beta chain or gamma/delta chain

Question 5

What is the structure of the TCR complex?

Answer 5

Contains the TCR, CD3+ Co-receptor which contains 4 (gamma, 2x episilon and delta) chains. It also contains 2 zeta chains and the CD4+/CD8+ receptor that binds to a Lck tyrosine kinase at its end intracellularly.

Question 6

Which type of TCR do not require MHC?

Answer 6

gamma/delta TCR chains

Question 7

Which part of the T cell binds to the polymorphic part of the MHC?

Answer 7

CD3

Question 8

Which part of the T cell binds to the non-polymorphic part of the MHC?

Answer 8

CD4/8

Question 9

What sorts of co-stimulation occurs to have stable association with the APC ? Which costimulatory action produces further B7 production in APC?

Answer 9

CD80/86 (B7.1/2) found on antigen presenting cells will bind to the CD28 found on T cells. A further co-stimulatory interaction between CD40 on APC and CD40L on the T-cell can also occur, which increases further production of B7 production.

Question 10

What is LcK?

Answer 10

This is a tyrosine kinase. It phosphorylates the ITAMs in the CD3 and zeta chains of the TCR complex, which begins a phosphorylation cascade. It leads to the intracellular release of Ca2+ which cause the activation of certain transcription factors that regulate the production of cytokines.

Question 11

Which chromosomes encode for HLA genes?

Answer 11

Chromosome 6

Question 12

Which HLA genes codes for MHC Class I?

Answer 12

HLA-1, HLA-2, HLA-3

Question 13

Which HLA genes code for MHC Class II?

Answer 13

HLA-DP, HLA-DQ, HLA-DR

Question 14

How many MHC variants are there?

Answer 14

There are 12 variants

Question 15

Describe the Class I MHC pathway

Answer 15

This is an endogenous pathway. The intracellular pathogen e.g. virus antigen enters the TAP of the endoplasmic reticulum. It is chopped into peptides which bind with the MHC I molecule also made in the reticulum. It is then transported out to the cell surface, which CD8 cytotoxic T cells will recognise and kill.

Question 16

Describe the Class II MHC pathway

Answer 16

This is an exogenous pathway. The extracellular pathogen is taken by phagocytosis or endocytosis. The protein compartments are degraded into peptides by proteases that are active in acidic pH of phagosomes/endosome. On fusion with vesicles containing MHC class II molecules (made in the ER), microbial peptides bind with the MHC Class II. This is transported into the cell for CD4 helper T cell recognition. Th cells secrete cytokines.

Question 17

Describe differences in peptide binding clefts of the 2 different MHC molecules

Answer 17

MHC Class I have shorter peptide bonding clefts from 8-10 amino acids. MHC Class II have longer 10-15 amino acid long peptide bonding clefts.

Question 18

Describe structure of Class I MHC

Answer 18

3 polymorphic alpha chains with a beta microglobulin 2 chain.

Question 19

Describe the structure of Class II MHC

Answer 19

A polymorphic 2 alpha and 2 beta chains

Question 20

Which cells present MHC I molecules?

Answer 20

All nucleated cells

Question 21

Which cells present MHC II molecules?

Answer 21

Antigen presentinc cells e.g. dendritic cells, macrophages, B cells, endothelial cells, thymus epithelium

Question 22

Where does peptide loading occur in MHC I peptides?

Answer 22

Endoplasmic reticulum

Question 23

Where does peptide loading occur in MHC II peptides?

Answer 23

Late endosomes and lysosomes