Phylogenetic tracing of Ia genes

Abstract

The I region of the mouse H–2 complex has been subdivided into five subregions (A, B, J, E, C) on the basis of serological and functional analyses of intra-MHC (major histocompatibility complex) recombinant strains¹. However, no serologically detectable specificities nor Ir genes have been localized to the I–E subregion of the H–2^b and H–2^S haplotypes. Attempts to identify I–E gene products of these haplotypes by chemical analyses have also been unsuccessful^2,3. Thus, the H–2 complex of these haplotypes seems not to express I–E subregion genes. In this case, alloantisera raised in ‘I–E- negative’ strains of mice against ‘I–E- positive’ mouse cells might contain, in addition to the usual alloantibodies, antibodies reactive with conserved portions of I–E molecules inherited from a hypothetical primordial gene (I–E₀) which may have existed long before the speciation of contemporary animals. Such antibodies would show extensive cross-reactions with the I–E homologues of various species of animals. Interspecies cross-reactions of anti-Ia mouse alloantibodies have indeed been observed. Although such a cross-reaction was first found between mouse I–A and rat Ia-homologues, subsequent studies indicated much broader and more frequent interspecies cross-reactions of anti-I–E antibodies^4–8. We have now expanded the demonstration of such interspecies cross-reactions to submammalian vertebrates. The possible basis of these unusual cross-reactions and its phylogenetic implication will be discussed.