Class I molecules with similar peptide-binding specificities are the result of both common ancestry and convergent evolution.

HLA class I molecules can be classified into supertypes associated with overlapping peptide-binding motifs and repertoires. Herein, overlaps in peptide-binding and T-cell recognition repertoires were demonstrated between mouse and human molecules. Since rodent and primate lineages separated before the current allelic variation of mouse and human class I molecules, these data demonstrate that supertypic specificities originated by convergent evolution. Phylogenetic and structural analyses demonstrated that convergent evolution also occurs amongst primates and within the human species, resulting from the selection of different pocket structures having similar specificity or independent repeated selection of the same pocket structure.