Lecture 7: MHC Molecules

Question 1

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Question 2

What is the MHC?

Answer 2

Major histocompatability complex

Question 3

How is the MHC related to transplant rejection?

Answer 3

MHC are large genomic regions which have thousands of genetic variants of transplantation antigens, so must be matched by tissue typing

Question 4

What are MHC molecules used for?

Answer 4

Used by the immune system to detect infections inside cells and cancers

Question 5

How does the arms race with pathogens affect MHC?

Answer 5

Drives high polymorphism

Question 6

What are the key details of classical MHC?

Answer 6

Highly polymorphic, present peptides to T cells, have wide tissue distribution, are conserved among all jawed vertebrates

Question 7

What cells are class I and class II MHC expressed on?

Answer 7

Class I: all nucleated cells
Class II: professional and facultative APCs

Question 8

What is different about non-classical MHC?

Answer 8

Differ in one or more of the classical attributes, usually derived from different times in evolutionary history

Question 9

What is the action of MHC?

Answer 9

Bond peptides within the cell and take them to be presented on the surface and recognised by T cells

Question 10

What’s the difference between MHC class I and MHC class II?

Answer 10

Class I: present to CD8 T cells (CTL)
Class II: present to CD4 T cells (Th)

Question 11

Why are CD4 and CD8 needed?

Answer 11

T cells need both TCR and receptor signalling for activation

Question 12

How do B cells signal to T cells?

Answer 12

B cells get antigens inside of them via receptor mediated endocystosis, which get turned into peptides, which then get presented by MHC to helper T cells

Question 13

What is the process of antigen presentation in MHC I molecules?

Answer 13

• protein enters the proteosome, and the antigenic peptide gets pumped into the ER lumen by TAPS
• MHC I is loaded with peptide and are taken to cell surface
• recognised by T cells which have CD8aB and aB TCR, which have granules of perforin and granzyme

Question 14

What does perforin do?

Answer 14

Makes a hole in the membrane

Question 15

What is granzyme?

Answer 15

Similar to caspase, induce apoptosis

Question 16

What sort of molecules can class II MHC recognise?

Answer 16

Bonds peptides from intravenously vesicles and extracellular space, so can include bacteria, parasites, and viruses

Question 17

What does the invariant chain of MHCII do?

Answer 17

Sits in the peptide binding groove of the class II so peptides in the ER don’t get loaded on

Directs class II invariant chain complexes to the late endosome, meets DM, helps optimise the the kind of peptides found on class II

Question 18

How does the invariant chain what is DO?

Answer 18

Looks like a class II molecules, binds to DM, changes breadth of peptide repertoire

Question 19

What does cross-presentation do?

Answer 19

Necessary to get Th for a CD8 response,
Cross presentation is so the CdCs can turn on and stimulate and activate CD8 cells

Question 20

What role do NK cells play?

Answer 20

Monitor the level of class I on the surface = too little, kill the cell, lack of class I is stress signal

Question 21

What is the structure of class II MHC?

Answer 21

2 similar chains:
- cytoplasmic tail
- hydrophobic transmembrane region
- 2 extracellular domains

Question 22

What is the structure of class I MHC?

Answer 22

Similar to Class II, but rearranged:
Protein beta 2 microglobulin and 3 extracellular domains

Question 23

How did invarient tryptophans give rise to MHC types?

Answer 23

Ancestor intradomain tryptophan and interdomain tryptophan is class II. Interdomain tryptophan on W gave rise to MHC I

Question 24

What do MHC binding grooves do?

Answer 24

Allows the peptides to extend out of the groove in class II, while the grooves are blocked at each end in class I

Question 25

In which way do TCRs bind over the MHC peptide complex?

Answer 25

CDR1 and CDR2 bind MHC, CD3 binds peptide, corrector’s CD4 and CD8 bind loop

Question 26

What are the 3 non classical MHC class II molecules?

Answer 26

DM: chaperone, peptide editor, non-polymorphic expressed in APCs
DO: binds and inhibits DM, non polymorphic, expressed in some APCs (B cells)
DQ2: no known function, monomorphic, expressed in langerhans cells (skin DCs)