Recent data suggest that the majority of HLA-A and-B alleles in human populations can be
grouped into four major supertypes, as defined by their broad peptide-binding specificities.
As discussed by John Sidney and colleagues, these data add to our understanding of the
evolutionary and biochemical processes involved in the generation of MHC polymorphism,
and suggest that HLA class I alleles may ultimately be reclassified on the basis of their
peptide-binding specificities.