Immune recognition of transplacentally acquired lymphoid allografts selects for increased major histocompatibility...

The extreme polymorphism of mammalian major histocompatibility (MHC) Class I and Class II alleles has been attributed to inbreeding avoidance, heterozygote advantage and pathogen driven selection for rare MHC alleles. However, MHC alleles can be classified into a limited number of allele supertypes based on the specificity of their peptide binding grooves (about 10 supertypes in the case of human MHC Class I alleles). The paradox is that if antigen presentation can be accomplished by a limited number of binding groove motifs, why are these loci so polymorphic? An unexplored driver of this complexity may be selection pressure to enhance the antigenicity and immune recognition of transplacentally acquired lymphoid allografts during pregnancy. The exchange of lymphoid cells between mother and fetus probably occurs in all pregnancies and may lead to fetal and/or maternal lymphoid microchimerism, a known cause of autoimmune disease. Natural selection may have favoured increased polymorphism at MHC Class I and Class II loci in order to improve immune surveillance of these cells and thereby reduce the incidence of maternal and fetal autoimmune disease. At the same time, selection may have favoured the retention of a limited set of allele supertypes which optimally present immunodominant antigens.