Major histocompatibility complex I and II

Question 1

Fxn of MHC ?

Answer 1

Present Antigen fragments to T cells and bind T-cell receptors (TCRs)

(meaning that TCRs recognise Ags when presented in the membrane of self- MHC molecules, then present them to T-cells)

Question 2

Structue of TCRs

Answer 2

Heterodimer composed of:
1) 2 glycoproteins: an α-chain and a β-chain
2) α and β chains posses variable (V) and constant (C) domains
3) 1 antigen-binding site
4) No hinge region –> conformation is rigid

Question 3

B- versus T-cell antigen receptors

* BCR, TCR

Answer 3

Question 4

HLA bounds to MHC I

Answer 4

HLA-A, HLA-B, HLA-C

* MHC I loci has 1 letter

Question 5

what type of HLA are bound to MHC class II ?

Answer 5

HLA-DR, HLA-DQ, HLA-DP

* MHC II loci has 2 letters

Question 6

Function of MHC class I?

Answer 6

present intracelluar antigen peptides to CD8+ Cytotoxic T cells –> Enodgenous (cytosolic) pathway

Question 7

Function of MHC class II

Answer 7

Present Extracelluar antigen peptides to CD4+ Helper T cells –> Exogenous (endocytic) pathway

Question 8

MHC I are expressed on?

Answer 8

All nucleated cells , APCs, platelets (except RBCs)

Question 9

MHC II are expressed on?

Answer 9

APCs only (DCs, B-cell, macrophages)

Question 10

T cells will only recognize antigens presented by their own MHC molecules –> this is known as ?

Answer 10

self-MHC restriction

Question 11

Antigen recognition by the CD4+ TH cells is class [I/II] MHC restricted?

Answer 11

MHC class II

Question 12

Antigen recognition by the CD8+ Tc cells is class [I/II] MHC restricted?

Answer 12

MHC class I

Question 13

What is bound to MHC I

Answer 13

TCR, CD8

Question 14

What is bound to MHC II

Answer 14

TCR and CD4

Question 15

Structure of MHC I

Answer 15

1) 1 long chain (α1,α2,α3) and 1 short chain (β2-microglobulin)
2) The α1 and α2 domains form a cleft region (peptide binding groove)

Question 16

structure of MHC II

Answer 16

1) heterodimer: 2 equal-length chains ( 2α, 2β)
2) At the N-terminal of both chains a peptide binding-celft –> peptide binding groove is formed by the pairing of the α1 and β1 chains

Question 17

What contributes to the diversity of limited MHC molecules in each individual?

Answer 17

Polymorphisim, polygeny and codominant experssion
1. MHC region is polygenic
2. MHC region isinherited as a haplotype (set of alleles)
3. MHC genes exhibit a codominant form of expression
- codominantly expressed ; both paternal and maternal gene products are expressed in the same cell

Question 18

what is responsible for the inhibition of MHC class I presentation?

Answer 18

block of internal protein synthesis

Question 19

What is responsible for the inhibition of MHC class II presentation?

Answer 19

Treatment w/ agents (e.g. chloroquine) that block enodcytic processing within the cell

* presentation of class II is unafected by protein synthesis inhibition

Question 20

Describe the pathway of Antigen presentation by MHC-I

Answer 20

Endogenous (cytosolic) pathway
1. Production of proteins by the cytosle
2. Proteolytic degradation of proteins by proteasome–> into peptides
3. Peptides are transported into the RER by a transport protein called TAP
4. At the same time the α chain and β2-microglobulin synthesised on ribosomes on the RER Bind–> forming class I molecules
5. class I molecule –> binds to Tapasin (TAP-associated protein)
6. Tapasin brings the TAP transporter into proximity with class I molecule and allows it to acquire an antigenic peptide
7. Antigenic peptide binds to MHC-I –> moves the cell membrane via the Golgi apparatus

 in summary: Antigen peptides loaded onto MHC-1 in RER after delivery via TAP

Question 21

How do Proteasome inhibitors induce apoptosis in tumour cells?

Answer 21

They degrade p53 (apoptosis proteins) –> accumulation of p53 and other regulatory proteins –> cell death via apoptosis

Question 22

Examples of Proteasome inhibitors in clinical use?

Answer 22

bortezomib,carfilzomib
- for multiple myeloma (under clinical trials for
leukemias)

Question 22

APCs that exhibit Cross-presentation of exogenous antigens

Answer 22

Dendritic cells

Question 23

Exaplin the Corss-presentation of exogenous antigens by DCs

Answer 23

1) Exogenous antigens are redirected to the endogenous presentation pathway
2) This allows for their presentation on MHC class I molecules and is essential for activation of naïve CD8+ T cells
3) This licenses DCs to activate cytotoxic T cells without themselves getting infected

Question 24

Describe the Exogenous pathway of antigen processing and presentation

Answer 24

In summary : Antigen loaded following release of invariant chain in an acidified endosome