Lecture 8 MHC

Question 1

Describe the structure of MHC class I molecules and their function

Answer 1

alpha chain has 5 domains, three extracellular (alpha 1-3), a transmembrane one and a cytoplasmic one
Antigen binding site formed by alpha 1 and 2 domains
Beta 2 domain stabilises structure
Class 1 molecules expressed on most nucleated cells
They present endogenous antigens to CD8+ T cells - CMI (cytotoxic)
Mainly viruses as they are intracellular parasites

Question 2

Describe structure and function of MHC class II molecules

Answer 2

The antigen binding site is formed by alpha 1 and beta 1 domains. Alpha 2 in between alpha 1 and the transmembrane domain. Beta 2 between beta 1 and transmembrane domain
Class 2 molecules expressed on professional APCs, Dendritic cells, macrophages and B cells
They present exogenous antigens to CD4+ T cells - humoral immunity (B cells - antibodies)

Question 3

What is MHC restriction

Answer 3

For foreign antigens to be recognised by TCR on either T helper or cytotoxic T cell the antigen must be present with MHC molecule, T cell recognises both MHC and antigen

Question 4

What are haplotypes

Answer 4

Allelic forms of MHC genes are inherited in tightly linked groups called haplotypes, Each indiviual inherits one haplotype from each parent

Question 5

What is the ideal number of MHC loci and why

Answer 5

6, because less than 6 means higher susceptibility of infection as body can not recognise as many pathogens as 6 loci. More than 6 however increases the risk of autoimmune disease as too many loci may kill self antigens.

Question 6

What is relative risk

Answer 6

Defined as chance of individual with disease associated MHC antigen has of developing disease compared with an individual who lacks that antigen

Question 7

Whats absolute risk

Answer 7

Chance an individual who possesses disease associated MHC antigen has of actually developing disease

Question 8

What type of T cells do MHC class molecules I and II present antigens to

Answer 8

MHC class I - Cytotoxic T cells
MHC class II - Helper T cell

Question 9

Describe T cell receptors

Answer 9

Glycoproteins found only on T cells
Two types - alpha/beta and gamma/delta
Any single cell will present either alpha/beta or gamma/delta
TCR always associated with CD3 molecules which are involved in regulation of T cell activation

Question 10

Describe TCR genes

Answer 10

Have V, D and J segments joined together VDJ which are the variable antigen binding site of TCR.
Constant domains coded by C exons
TCR antigen binding regions as diverse as Ig ones

Question 11

Describe production of TCR genes

Answer 11

Three gene loci, A/D used for alpha and delta, initial choice of A or D determines whether chain is Alpha/beta or gamma/delta
V and D bind together and the rest of Vs deleted as well as all J, C and Ds apart from closest ones
DNA rearranged and transcribed. RNA splicing occurs to get rid of undesired J so only VDJC remain and is translated