How does MHC variation due to multigene families and allelic polymorphism influence the antigens that a person's T cells can recognize?

Question

What will be an ideal response?

Answer 1

T cells recognize peptide antigens in the form of peptide:MHC complexes, which they bind using their T-cell receptors. To bind specifically, the T-cell receptor must fit both the peptide and the part of the MHC molecule surrounding it in the peptide-binding groove. (i) Because each individual expresses a number of different MHC molecules from the MHC class I and class II multigene families, the T-cell receptor repertoire is not restricted to recognizing peptides that bind to just one MHC molecule (and thus all must have the same peptide-binding motif). Instead, the T-cell receptor repertoire can recognize peptides with different peptide-binding motifs during an immune response, increasing the likelihood of antigen recognition and, hence, T-cell activation. (ii) The polymorphism in MHC molecules is localized to the regions affecting T-cell receptor and peptide binding. Thus, a T-cell receptor that recognizes a given peptide bound to variant ‘a' of a particular MHC molecule is likely not to recognize the same peptide bound to variant ‘b' of the same MHC molecule. Polymorphism also means that the MHC molecules of one person will bind a different set of peptides from those in another person. Taken together, these outcomes mean that because of MHC polymorphism, each individual recognizes a somewhat different range of peptide antigens using a different repertoire of T-cell receptors.