Question

Comparing MHC I a-chain and b2-microglobulin (b2-MG) in a family of six, including mom, dad and two daughters and two sons:

1) Among the six family members, which pair is more likely to find similarity between the two for possible transplant, father/mother, mother/daughter, father/son, father/daughter, or siblings? Why?

2) Deficiency in b2-MG was reported in 2 siblings. How does the b2-MG deficiency affect their immune system?

3) Hypothetical question: if an individual had genetic alterations in MHC-I, resulting in deletion of HLA-B, C, E, F and G gene loci, leaving only HLA-A intact, what would you expect of the immune system in this individual and why? Would this individual have similar phenotype to the one seen with the deficiency in b2-MG?

Answer 1

1) The HLA-matched siblings will have a 95-100% chances of success. It is because the siblings resemble more closely in their tissues as compared to the other possibilities.

2) In the absence of b2-MG , the class I MHC chain is not expressed on the cell membrane and hence have a deficiency of cytotoxic T cells( which play an important part in acquired immunity).

3) In case of deletion of HLA-B,C,D,E,F and G gene loci, with HLA-A intact, the immune system will become weak. Its because the loss of the above genes will result in the failure of formation of the transmembrane glycoprotein, which is reffered to as alpha,or the heavy chain. In the absence of this hevay chain,the MHC won't be able to interact with the CD8membrane molecule present on cytotoxic Tcells. Hence, the acquired immunity of the individual that is due to these cells, decreases.

Yes, the individual will have similar phenotype as the one seen with b2-MG deficiency. This is beacuse of the lack of interaction with the cytotoxic T cell( as explained above).