okamura kazuhiko

The elucidation of the complete peptide-binding domains of the highly polymorphic shark MHC class I genes offered us an opportunity to examine the characteristics of their predicted protein products in the light of the latest advance in the structural studies of the MHC class I molecules. The results suggest that the fundamental characteristics in the T-cell recognition of the MHC class I molecule/peptide complex are expected to have been established at the early stage of the vertebrate evolution. The elucidation of the typical classical class I molecules from fishes and also of some MHC class I-related molecules may help us to explore the common denominator of the ancient class I molecules.

We report the isolation and extensive analysis of highly polymorphic MHC class I genes from sharks (Triakis scyllia), which belong to the most primitive vertebrate group with jaws, the cartilaginous fish. Predicted complete peptide-binding domains showed retention of the critical amino acid residues that would interact with antigenic peptide termini and revealed extensive allelic polymorphisms comparable to those of classic human MHC class I molecules. Mosaic structures were apparent in these domains, suggesting recombinational mechanisms to create allelic diversity. The present study demonstrates the establishment of the basic strategy for antigen-presentation employed by MHC class I molecules and documents complete divergence of two polymorphic MHC classes at a phylogenetically primitive stage of vertebrate evolution.

We have analyzed the genomic genes and the mRNA that encode MHC class I molecules in cyprinid fishes, namely, the ginbuna crucian carp (Carassius auratus langsdorfii) and the carp (Cyprinus carpio). The presence of several distinct class I genes was revealed in the genome of cyprinid fishes, and distinct class I genes that are expressed in carp cells were identified. The sequences of the alpha3 domain of these class I genes are relatively well conserved, whereas the sequences of the respective alpha1 and alpha2 domains have diverged from one another. A comparison of the sequences expressed in carp with the sequences of the human classical class I molecules revealed that several amino acids in the peptide-binding region, including those that have been proposed to interact with antigenic peptide termini, are highly conserved. The present study demonstrated a dynamic expansion of the genes that encode MHC class I molecules in teleost fish whose ancestor branched off from the vertebrate line leading to mammals more than 400 million years ago.