Immunogenetics

Question 1

Factors responsible for enormous range of antibody specificity

Answer 1

1) H and L variable and constant regions are coded by different genes
2) rearrangement: any one of the many variable region genes can be linked to a single constant region gene, thereby conserving DNA
3) additional J (joining) sequence, linking the Lv to Lc, is required during formation of L chain
4) formation of H chain requires D (diversity) sequence to link Hv to J sequence. These then fuse with Hc
5) late rearrangement of “class genes” in the Hc region dictates class switching to A and G subclasses via T-cell cytokines

Question 2

Explain random selection in the context of antibody genetics

Answer 2

Each B cell randomly selects from the variety of V, D, and J germ line genes available resulting in a large number of structural possibilities for the Lv and Hv epitope binding regions. Primarily responsible for antibody diversity

Question 3

Characteristics of HLA class I

Answer 3

• glycoprotein
• found on all nucleated cells
• encoded by three gene regions A, B, C
• link to cytotoxic T cells through CD8 molecule
• each HLA molecule can bind several different peptidal epitopes
• two chains (a and b2)
• a chain has three segments, a1 and a2 are peptide binding locations, bind peptides containing 8-10 AA
• a3 is CD8 binding site
• b2 chain is an invariant protein

Question 4

Characteristics of HLA class II

Answer 4

• glycoprotein
• found on dendritic cells, macrophages, activated T and B cells
• encoded by three gene regions: DP, DQ, DR
• linked to Th cell via CD4
• single class II molecule can bind several different epitopes
• a and b chains each with two domains
• a1 and b1 are epitope binding sites, bind 13-18 AA
• b2 binds CD4

Question 5

Polymorphism

Answer 5

Many alleles of class I and II are present at each locus on chromosome 6 and are the major obstacles to organ transplantation

Question 6

How many gene regions code for HLA class I and what are they called?

Answer 6

3 regions: A, B, and C

Question 7

The alpha-3 chain on HLA class I binds:

Answer 7

CD8 on cytotoxic T cells

Question 8

The alpha-1 and alpha-2 chains on HLA class I bind:

Answer 8

peptides, 8-10 AAs long

Question 9

Which chain on HLA class I is invariant?

Answer 9

The beta-2 chain

Question 10

Where is HLA class I found?

Answer 10

All nucleated cells

Question 11

The V and J gene segments for the synthesis of TCR-alpha are associated with which chromosome?

Answer 11

14

Question 12

The V, J, and D gene segments for the synthesis of TCR-beta are associated with which chromosome?

Answer 12

7

Question 13

What is the most important genetic difference between TCR-alpha and TCR-beta?

Answer 13

beta includes a diversity (D) regions and alpha does not.