Major Histocompatibility Complex

Question 1

What is the function of MHC?

Answer 1

• marks host cells as self

- antigen presentation to induce an immune response

Question 2

What are HLA?

Answer 2

Human Leukocyte Antigens = MHC specific to humans

Question 3

What are the types of HLA loci?

Answer 3

Class I = ABC
Class II = D (DP, DQ, DR)
Class III

Question 4

Describe the function of Class I HLA molecules.

Answer 4

• located on the surface of all nucleated cells to serve as a “self” marker
• present peptides to CD8+ killer T cells

Question 5

Describe the function of Class II HLA molecules.

Answer 5

• located on the surface of antigen presenting cells (dendritic cells, monocytes, macrophages, B cells)
• present peptides to CD4+ helper T cells

Question 6

What is unique about surface markers of antigen presenting cells?

Answer 6

express both Class I and Class II MHC molecules

Question 7

Compare mouse and human MHC genes.

Answer 7

similar structures and functions

Question 8

Describe the gene structure of MHC genes.

Answer 8

• all MHC genes are located on chromosome 6, except for B2-microglobulin invariant chain for Class I molecules
• Class II is located 5’ to Class I
• gene products are shuttled to the ER for association with the peptide and then shuttled to the surface

Question 9

Describe the structure of the final MHC Class I gene product.

Answer 9

• all 3 class I loci code for an alpha chain (3 domains)

- B2-microglobulin chain from another chromosome is invariant and associates with the alpha chain

Question 10

Describe the domains of a Class I MHC.

Answer 10

alpha 1 and alpha 2 form a peptide-binding cleft
- 2 alpha helices
- 2 beta pleated sheets for a platform for the peptide
alpha 3 anchors the alpha chain to the membrane
B2 domain is a beta pleated sheet

Question 11

Describe the structure of the final MHC Class II gene product.

Answer 11

• each class II loci codes for an alpha chain and a beta chain (DPalpha and DPbeta)
• alpha chain (2 domains) and beta chain (2 domains) associate together at the surface

Question 12

Describe the domains of a Class II MHC.

Answer 12

• alpha 1 and beta 1 form the peptide-binding cleft

- alpha 2 and beta 2 have transmembrane portions to anchor them to the cell

Question 13

What is the difference in peptide binding between class I and class II?

Answer 13

class I binds to shorter peptides (8-10 AA), while class II binds to longer peptides (13-17 AA)

Question 14

What is the purpose of anchor sequences?

Answer 14

• provide conserved AA regions for the peptide to associate with peptide-binding cleft
• by burying the anchor sequence onto the peptide cleft, the varying AA sequences are available for recognition by TCR

Question 15

What are the class I anchor sequences?

Answer 15

• C terminal
• Tyrosine
• Hydrophobic AA
• N terminal

Question 16

What are the class II anchor sequences?

Answer 16

• C terminal
• hydrophobic AA
• negative charged
• basic
• hydrophilic AA
• N terminal

Question 17

Describe the genetic expression of MHC genes.

Answer 17

co-dominant

• both maternal and paternal haplotypes are expressed
• example: for a host cell, you would have both maternal and paternal alleles/chromosomes expressed for HLA-ABC
• example: for an APC, you would have both maternal and paternal allele/chromosomes expressed for HLA-ABCD

Question 18

Describe the polymorphic property of MHC genes.

Answer 18

For each MHC locus, there are over 800 possible alleles. Hence, between individuals in a population, there is a high variability in nucleotide sequence => high variability in AA sequence

Question 19

Where are MHC polymorphisms typically located on the final gene product? What function does this serve?

Answer 19

• located on the peptide-binding cleft at specific sites

- high variability in MHC gene products => ability to bind many different peptides

Question 20

Define MHC Restriction.

Answer 20

TCR must recognize the peptide AND the MHC molecule (via alpha helices)

Question 21

What part of the TCR recognizes the MHC?

Answer 21

CD4 or CD8 binds to TCR as a coreceptor to recognize their associated MHC (class II and I, respectively)

Question 22

List the steps involved after TCR-CD8+ recognizes a peptide-MHC complex.

Answer 22

1. recognition

2. kills cell (cytotoxic)

Question 23

List the steps involved after TCR-CD4+ recognizes a peptide-MHC complex.

Answer 23

1. recognition

2. produces cytokines (helper T)