Question

MHC has a large number of different alleles at each locus. Where are most of the polymorphic amino acid residues located in MHC molecules, and why is the location important?

Answer 1

Polymorphism in the MHC is clustered in short stretches, largely within the membrane-distal alpha 1 and alpha 2 domains of class I molecules and   in the alpha 1 and beta 1 domains of class II molecules. These domains form the peptide-binding groove, where peptides from different protein bind after processing in cytoplasm and gets displayed on the surface of cell.

The location of so many polymorphic amino acids within the binding site for processed antigen/peptides strongly suggests that allelic differences contribute to the observed differences in the ability of MHC molecules to interact with a given peptide ligand. Therefore, these polymorphic amino acid residues help the MHC molecules to bind with different types of antigen entering the cell.