Major Histocompatibility Complex

Question 1

What chromosome contains the MHC in humans?

Answer 1

Short arm of chromosome 6

Question 2

What are the two classes of MHC? What sets of HLA genes are associated with each class?What do these individual HLA genes actually encode for?

Answer 2

1. Class I: HLA-A, HLA-B, HLA-C
2. Class II: HLA-DP, HLA-DQ, HLA-DR
   The individual HLA genes encode for the alpha chain of the MHC class I molecule, and the alpha and Beta chainst of the MHC class II molecule

Question 3

How are MHC inherited and expressed?

Answer 3

Each person has two haplotypes (two sets of MHC) with one paternal set and one maternal set expressed in a codominant gene fashion (both paternal and maternal genes are expressed.)

Question 4

How many MHC molecules can an individual make?

Answer 4

Class I: 2 MHC haplotypes x 3 HLA types=6

Class II: 2 MHC haplotypes x 4 HLA types (DR has two Beta chains, either of which can pair with the alpha chain)=8

Question 5

Name the HLA haplotype associated with each of the following diseases: Multiple sclerosis, Type I diabetes, Rheumatoid Arthritis, Hashimoto disease, Hemochromatosis, Graves disease, Seronegative spondyloarthropathies (eg. ankylosing spondylitis, Reiter syndrome)

Answer 5

MS: HLA-DR2
Type 1 Diabetes: HLA-DR3/DR4
RA: HLA-DR4
Hashimoto:DR3/DR5
Hemochromatosis: HLA-A3
Graves disease: HLA-B8, HLA-DR3
Seronegative spondyloarthropathies: HLA-B27

Question 6

What is the importance of MHC classes I and II proteins?

Answer 6

Enable T cells to recognize foreign antigens

Question 7

What is the structure of MHC class I?

Answer 7

Structure=1x (a heavy chain) + 1x (B2-microglobulin)

Question 8

Describe the alpha heavy chain’s structure. Where is the peptide binding groove?

Answer 8

Three extracellular domains (a1 and a2 form the peptide-binding groove) and a13 anchors the protein to the surface of the cell by a single transmembrane domain

Question 9

The Beta-2 microglobulin is not encoded by a gene in the MHC region. What is its function?

Answer 9

Promotes proper folding and stabalizes MHC class I expression on the cell surface

Question 10

What are MHC class I proteins and where are they found?

Answer 10

Membrane glycoproteins on the surface of most nucleated cells and platelets

Question 11

What cells lack MHC class I proteins?

Answer 11

Red blood cells, neurons, and some tumor cells

Question 12

What is the function of MHC class I proteins?

Answer 12

They bind peptides derived from intracellular proteins (both self and foreign) and present them to cytotoxic T lymphocytes (CTLs)

Question 13

How do proteins become associated with MHC class I molecules?

Answer 13

Proteins in cytosol are routinely degraded to peptides and transported via a peptide transporter (TAP complex) into the endoplasmic reticulum, where they bind to newly synthesized HLA class I proteins

Question 14

What are sources of foreign proteins associated with MHC class I molecules? What happens to cells presenting foreign antigens?

Answer 14

Viruses, intracellular bacteria and parasites, or neoantigens (ie, the cell is a tumor cell). These cells are lysed by CTLs

Question 15

What is the structure of MHC class II molecules?

Answer 15

Structure= 1 alpha chain + 1 Beta chain

Question 16

Describe the structure of the alpha and beta chains. Where is the peptide binding groove located?

Answer 16

Each has two extracellular domains (alpha 1 and beta1) and one transmembrane domain (alpha 2 and Beta2). Peptide-binding groove is formed by the alpha1 and Beta1 extracellular domains of each chain

Question 17

Where are the MHC class II molecules expressed?

Answer 17

Antigen-presenting cells–monocytes/macrophages, dendritic cells, B lymphocytes, Langerhans cells, activated T cells, and activated endothelial cells

Question 18

MHC class II molecules are cell surface proteins. What is their function?

Answer 18

Bind and present exogenous peptides to CD4+ helper T lymphocytes

Question 19

How are MHC class II molecules loaded with peptides?

Answer 19

Vesicles containing endocytosed and cleaved extracellular protein fragments fuse with vesicles containing MHC class II molecules. In these vesicles, they are loaded onto MHC class II and are transported to the surface.

Question 20

What prevents MHC class II molecules from binding peptides before fusion with vesicles containing endocytosed antigen?

Answer 20

The invariant chain blocks the peptide binding groove of MHC class II molecules as it is transported through the cell. The invariant chain is degraded within the vesicle that contains processed antigen for loading.

Question 21

What is the major histocompatibility complex (MHC) also known as human leukocyte antigen (HLA complex)?

Answer 21

Sets of highly polymorphic genes, whose final protein products regulate the immune response, especially antigen (Ag) presentation to T cells