L4: Major Histocompatability Complex

Question 1

What is the MHC?

Answer 1

a large cluster of genes encoding specialized glycoproteins. Has many functions but for us it has a role in antigen presentation to T cells.

Question 2

How is antigen recognition by T cells different from antibody:antigen recognition?

Answer 2

T cells ONLY recognize peptides bound to MHC molecules

Question 3

How are class I and class II MHC different?

Answer 3

???

Question 4

How many different peptides can each MHC bind to?

Answer 4

many different peptides

Question 5

A peptide is 15 AA’s long, can it bind to Class I or Class II MHC, or both?

Answer 5

It can only bind to Class II because Class I MHC will only bind to peptides betwen 8-10 AA’s in length because they are closed at the ends whereas Class II are open.

Question 6

What is binding of MHC class I molecules stabilized by?

Answer 6

regions in the basement of the cleft that induce fit.
AND
Contacts betweeen A-terminal ends and C-terminal ends of the peptice and invariant sites found at the ends of the binding groove. (this is only true of Class I)

Question 7

Which class of MHC follows the hotdog in a bun model of binding?

Answer 7

Class II. It has open ends, allowing it to bind to very long peptide chains.

Question 8

How is peptide binding stabilized in class II MHC molecules?

Answer 8

by contacts between the peptide backbone and conserved residues that line the binding groove

Question 9

Which class MHC molecule has more restricted binding?

Answer 9

Class I. It is restricted to smaller peptides

Question 10

What is the TAP transporter complex?

Answer 10

After proteosomes break proteins into peptide fragments, the TAP transporter moves some of those fragments from the cytosol to the ER lumen, and ultimately loaded onto Class I MHC molecules.

Question 11

Can an MHC class I molecule without an peptide bound to it move to the golgi then the cytoplasm?

Answer 11

No. It will degrade rather rapidly in the ER if it doesn’t bind to a peptide

Question 12

What type of MHC is recognized by CD8 T cells?

Answer 12

Class I MHC.

Question 13

What types of cells synthesize class II MHC?

Answer 13

antigen presenting cells and thymus cells

Question 14

What types of cells synthesize class I MHC?

Answer 14

almost all nucleated cells.

Question 15

What prevents proteosomal derived peptide chains from binding to MHC class II molecules?

Answer 15

The invariant chain, which is bound to the class II MHC until it is in a vesicle, at which point it breaks down but leaves CLIP fragment in the binding groove. Once the vesicle fuses with an antigen filled endosome, HLA-DM removes CLIP fragment and peptides bind to the groove and are presented on cell surface.

Question 16

What type of MHC do CD4 T cells bind to?

Answer 16

Class II.

Question 17

What type of peptides are usually found in class I MHC: intracellular or extracellular?

Answer 17

Intracellular. Via proteosomal degradation and ER.

Question 18

What is the enzyme that allows release of the CLIP fragment in class II MHC?

Answer 18

HLA-DM

Question 19

What type of peptides are usually found in class II MHC: intracellular or extracellular?

Answer 19

extracellular pathogens. Invariant chain prevents intracellular pathway from occurring.

Question 20

What type of peptide is usually bound to MHC: self or pathogen?

Answer 20

Usually only self molecules, except in times of infection.

Question 21

What type of tissue is low in MHC class I molecules?

Answer 21

Neural tissue. Really don’t want CD8 T cells attacking infected neural cells.

Question 22

Which type of pathogens are Ab-mediated immune responses best for: intracellular or extracellular? What type of T cell helps? What class MHC?

Answer 22

Ab-mediated immune responses are best for clearance of extracellular pathogens, which are bound to Class II MHC, which illicit responses from CD4 T cells.

Question 23

Which type of pathogens are CD8 T cell-mediated immune responses best for: intracellular or extracellular? What class MHC?

Answer 23

Intracellular pathogens are best cleared by CD8 T-cell mediated responses, which use Class I MHC

Question 24

Define Polygeny.

Answer 24

Existence in the genome of several different genetic loci encoding structurally similar proteins of identical functions

Question 25

Define polymorphism.

Answer 25

existence of two or more forms of a given gene within the population

Question 26

What are the two most polymorphic sets of genes in the body? Why?

Answer 26

MHC class I and II.
Each person inherits 3 MHC class I genes on each chromosome and at least 3 class II genes on each chromosome.

Question 27

What are the genes for Class I MHC?

Answer 27

HLA-A, HLA-B, HLA-C

Question 28

What are the genes for Class II MHC? In which of these can you inherit multiple beta chains? Is there an advantage to this?

Answer 28

HLA-DP, HLA- DQ, HLA-DR.

HLA-DR you can inherit 1 or 2 beta chains.
Having more is a huge advantage because you can create more polymorphisms of the MHC molecule so you can present a wider variety of antigens.

Question 29

Why don’t you see much variability in binding of MHC class I molecules with various alpha chains?

Answer 29

There is little variability between the HLA-A genes and few polymorphisms.

Question 30

If you inherit homozygously at all positions of the MHC class I and class II molecules, how many different types of MHC can you make of each?

Answer 30

only 3 different class I and 3 class II. This is the minimum possible.

Question 31

If a person inherits heterozygously for all MHC class I genes, how many different MHC class I molecules can they produce? What is the max if this happened for class II?

Answer 31

6 for Class I all hetero

48 for Class II all hetero