Jitt #4 Advances in Immunology The HLA System

Question 1

HLA

Answer 1

Human Leukocyte system. The human version of the major histocompatibility complex.

Question 2

Class I HLA Chain structure

Answer 2

Class I genes encode for the alpha polypeptide chain; the beta chain is encoded on a gene on chromosome 15 (the beta2-microglobulin gene)

Question 3

Alpha Chain Class I

Answer 3

Has five domains; two peptide binding regions (alpha-1, alpha-2); one immunoglobulin- like domain (a3), the transmembrane region, and the cytoplasmic tail.

Question 4

Class II HLA Chain structure

Answer 4

Class II genes encode for both alpha and beta polypeptide chains.

Question 5

On what types of cells are Class I HLA expressed on? Class II HLA?

Answer 5

Class I HLA are expressed on most somatic cells, with some differences depending on tissue, while Class II genes are mostly expressed by (B cells, activated T cells, macrophages, dendritic cells, and thymic epithelial cells.

Question 6

What cytokine upregulates the amount of Class II HLA on other cells?

Answer 6

Interferon Gamma

Question 7

What is the role of ubiquitin in waste disposal and recycling?

Answer 7

Ubiquitin is responsible for marking worn out proteins for destruction (and pathogenic material like HIV). Proteasomes chop these fragments up.

Question 8

TAPs

Answer 8

Transporters associated with antigen processing. TAP1 and TAP2 proteins interact to form a channel for transporting peptides across the membrane of the endoplasmic reticulum. Peptides released by proteasomes bind the TAP. TAP mediates the binding of peptides to Class I HLA. HLA II are not loaded with peptides in the ER. HLA II binds to proteins produced in the ER. HLA II are then sent off in membraneous vesicles and in the cytoplasm, they fuse with endosomes. Proteases in the endosome degrade proteins in to peptide fragments. These peptide fragments are then able to bind in the groove of HLA II and are able to be presented to the cell surface.

Question 9

What three regions in the V region are responsible for diversity among T cells?

Answer 9

CDR1 & CDR2 (Both inherited in the germline) CDR3 (inherited somatically during maturation)

Question 10

The expression and binding of which HLA corresponds to either CD8+ differentiation or CD4+ differentiation?

Answer 10

Binding of HLA I corresponds to CD8+ differentiation, while the binding of HLA II corresponds to CD4+ differentiation.

Question 11

Cortical Epithelial Cells.

Answer 11

First region of the thymus. This is the first opportunity that thymocytes can match their receptors with the abundant HLA peptides on cortical epithelial cells

Question 12

Medullary APC stage

Answer 12

Binding of T - Cells with APC causes apoptosis of thymocytes. This is a major stage where reactivity to self is tested.

Question 13

In what stage does negative selection and self reactivity occur?

Answer 13

The Medullary stage.

Question 14

What is the role of interferon gamma in the maturation of T cells?

Answer 14

It binds to regulatory regions of selected genes (Class II, proteasomes) leads to increased expression.