TcR and MHC interactions

Question 1

What is MHC restriction?

Answer 1

This is where T cells will only recognise specific peptides presented by specific MHC molecules.

Question 2

What cluster of genes encode MHC’s?

Answer 2

HLA - human leukocyte antigens
the 2 terms can be used interchangeably.

Question 3

What are the four genes that encode MHC1?

Answer 3

HLA-A, -B, -C = encode the three alpha domains and are found in the same part of the genome. Each alpha domain has its own alpha chain with the B2-microglobulin. The alpha areas can change but the beta domain will always stay the same.
The beta 2 microglobulin is found in a different part of the genome on a different chromosome.

Question 4

What is the structure of a MHC1 molecule?

Answer 4

alpha 1 and alpha 2 domains form the peptide binding region. They are two alpha helices that bend round in order to hold the peptide and they are polymorphic domains.
the peptide binding cleft contains a short AA peptide that helps with specificity.
They can hols peptides up to 8-10 AAs in length.

Question 5

What genes encode MHC2?

Answer 5

There are three class 2 molecules:
- HLA-DP
- HLA-DQ
- HLA-DR
Each class has an alpha and a beta gene, the nomenclature therefore adds an A or a B to the end of the gene name, giving 6 genes
- they are encoded by the same area in the MHC genome

Question 6

What is the structure of MHC2?

Answer 6

• can hold peptides 13-24 AA’s in length, showcasing larger peptides to the T helper cells.
  -Alpha 1 and beta 1 are the polymorphic regions

Question 7

How are Ags processed and presented by MHC1?

Answer 7

MHC1 recognises intracellular pathogens such as viruses.
The antigen is broken in the proteosome, moved to the endoplasmic reticulum and transported into it by the TAP mechanism, the peptides are them bound to an MHC1 molecule, transported to the cell surface through the Golgi, ready for the cytotoxic T cell (CD8+) which will introduce apoptosis.

Question 8

What is located next to the TcR’s and what is their function?

Answer 8

CD3 complex sits either side of the TcR and have longer transmembrane tails.
On the tails there are ITAM’s (immuno receptor tyrosine based activation motifs) that send a cascade of signals to the nucleus and DNA to increase the transcription of specific genes.

Question 9

What happens once a CD4+ Th molecule on a TCR binds with the peptide on an MHC2?

Answer 9

The binding of the CD4 initiates the signal.
The Lck molecule (kinase) gets activated, it phosphorylates the ITAMs (adds a phosphate group). Phosphorylation causes signal cascades.

Question 10

What is the main difference between CD8 and CD4?

Answer 10

CD8 kills
CD4 recruits