THE EVOLUTIONARY ORIGIN OF THE MAJOR HISTOCOMPATIBILITY COMPLEX - POLYMORPHISM OF CLASS-II ALPHA-CHAIN GENES IN THE CARTILAGINOUS FISH

T cells recognize antigen (Ag) in the tor-m of peptides bound to the m ajor histocompatibility complex (MHC) molecule. One of the important i ssues in evolutionary immunology is to identify the stage in phylogeny when this mode of Ag recognition emerged. At present, there is a cons iderable controversy as to whether the cartilaginous fish have the bon a fide MHC. In our previous study, we showed that the nurse shark, a m ember of the cartilaginous fish, has (a) gene(s) capable of encoding M HC class II alpha chains. In the present study, we examined the polymo rphism of nurse shark MHC class II alpha chain genes designated Gici-D AA and Gici-DBA using the polymerase chain reaction. The Gici-DAA and Gici-DBA genes had six and five alleles, respectively, and individual alleles usually differed by multiple nucleotides. In addition, most of the nucleotide substitutions were located at the putative Ag-binding sites, where non-synonymous substitutions occurred more frequently tha n synonymous substitutions. The fact that the Gici-DAA and Gici-DBA ge nes display a polymorphism pattern essentially similar to that of mamm alian MHC genes playing a major role in Ag presentation suggests that the cartilaginous fish have the bona fide MHC. Thus, the MHC-peptide-b ased T cell recognition system appears to have arisen at or before the emergence of the cartilaginous fish.