Major Histocompatibility Complex

Question 1

What is the physiological function of MHC Class I and Class II?

Answer 1

Present peptides to T-lymphocytes

Question 2

What are the three Class I HLA loci?

Answer 2

HLA-A
HLA-B
HLA-C

Question 3

Which are the three Class II HLA loci?

Answer 3

HLA-DR
HLA-DQ
HLA-DP

Question 4

What is the role of Class III HLA?

Answer 4

These are genes that happen to reside in MHC regions but do not present antigen to T-lymphocytes

Question 5

Which cells have Class I HLA? To which cells do they present antigen?

Answer 5

These molecules are present on virtually all nucleated cells and present antigen to CD8+ T lymphocytes.

Question 6

Which cells have Class II HLA? To which cells do they present antigen?

Answer 6

Professional APCs: B-cells, DCs, and macrophages.

They present antigen to CD4+ lymphocytes

Question 7

Describe the composition of MHC Class I

Answer 7

Alpha 1 and alpha 2 domains make up a binding cleft
Alpha 3 domain anchors into the plasma membrane
Beta2 microglobulin associates non-convalently

Question 8

How do HLA-A, HLA-B and HLA-C differ from one another?

Answer 8

The alpha chains are specified by different alleles.

The beta-2 microglobulin is constant in all of the molecules

Question 9

What percent of the alpha chain is carbohydrates?

Answer 9

10%

Question 10

What part of the alpha protein traverses the cell membrane?

Answer 10

The c-terminal end (of alpha 3 domain)

Question 11

Describe the structure of MHC Class II

Answer 11

Alpha chain and beta chain- each anchored into the cell membrane

Question 12

What length peptides are presented by Class I MHC?

Answer 12

MHC Class I molecules bind short peptides of about 9 amino acids in length (variability is 8-10)

Question 13

What length peptides are presented by Class II MHC?

Answer 13

MHC Class II molecules bind longer peptides of 13-17 amino acids in length

Question 14

Describe the sequence similarities of peptides bound to an MHC class I molecule

Answer 14

Although sequences do not need to be all that similar, the second residue needs to be aromatic (Y) and the last residue needs to be hydrophobic.

These conserved residues are called “anchor” residues

Question 15

Describe the sequence similarities of the peptides bound to a class II molecule

Answer 15

The anchor residues that bind a particular MHC class II molecule do not need to be identical but are always related (basic, hydrophobic, negatively charged etc)

Question 16

Every different cell that expresses MHC will have how many different MHC’s being expressed?

Answer 16

12 total: 2x HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, HLA-DP

You have 6 different kinds of class I and 6 different kinds of Class II MHC expressed on a cell. Each individual expresses in a CO-DOMINANT fashion the class I and class II genes of both the maternal and paternal chromosome 6

Question 17

The best donor is of what age and gender?

Answer 17

Young males.

Question 18

Discuss polymorphism in MHC Class I and II genes

Answer 18

CLass I has huge polymorphism seen in all three genes (569-1431 different alleles are seen throughout the population!)

ClassI has less polymorphism, with the notable exception being DRB

Question 19

What does MHC restriction refer to?

Answer 19

A specific T cell response to antigen on cell surfaces depends not on recognition of the antigen alone, but on recognition of an antigenic peptide in the groove on an MHC molecule on the cell surface.

Question 20

CD4+ T helper cells recognize antigen presented by which class of MHC?

Answer 20

Class II

Question 21

CD8+ cytotoxic T cells recognize antigen presented by which class of MHC?

Answer 21

Class I