MHC POLYMORPHISM AND PARASITES

The major histocompatibility complex (MHC) Polymorphism is marked by t he existence of allelic lineages that are extremely old, having been p assed from one species to another in an evolutionary line of descent. Each species has several of these lineages and many of their more rece nt derivatives, the actual alleles. The lineages are separated by larg e genetic distances and are characterized by the presence of short seq uence motifs which, at the protein level, have remained virtually unal tered for over 40 million years. Several explanations for the MHC poly morphism have been proposed. We argue that the only one consistent wit h the entire body of knowledge about the MHC is an explanation based o n the immune response to parasites. Furthermore, we propose that paras ites coevolving with their hosts have had a major influence on MHC pol ymorphism, whereas parasites that switched hosts recently and became v ery virulent have had little effect. The latter category includes micr o- and macroparasites responsible for the major human infectious disea ses. This hypothesis explains why no convincing association between hu man leucocyte antigen (HLA) alleles and resistance to infectious disea se can thus far be documented, and indicates the direction in which th e search for such associations should be taken.