岡村 和彦

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 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.

The nucleotide sequence of a 4621 base pair fragment of DNA, from a position upstream of D(SQ52) to the Smu region within immunoglobulin heavy-chain gene loci of Suncus murinus was determined. The sequence contained one D gene, three J(H) genes and an enhancer. Suncus murinus is an insectivore and is one of the most primitive mammals. Both primates and rodents are thought to have originated from insectivores and to have evolved separately. We also determined the nucleotide sequence of a region between human J(H) genes and the enhancer which has not previously been reported. Thus, the sequences of the entire region from each of the three species, Suncus murinus, human and mouse are now available. Comparison of the nucleotide sequence of this region between these three species indicated that D and J(H) genes, consisting of coding and signal regions, are highly conserved. Moreover, although extensive sequence homology in the region between J(H) and Smu was observed between mouse and human, only core portions of the enhancer region of Suncus murinus exhibited homology to those of mouse and human. Sequence conservation Of J(H) genes in Suncus murinus, mouse and human was observed not only at the amino-acid level, but also at the nucleotide level, including the third letters of the codons. It is suggested that J(H) genes may play a role in the metabolism of the DNA and/or RNA.