Limited polymorphism in the HLA-DOA gene

The HLA-DO molecule, a heterodimer consisting of two novel members of the c lass II gene family, DOA and DOE, has recently been suggested to function a s an important modulator in the HLA class II restricted antigen presentatio n pathway by interaction with the HLA-DM molecule. In this study we have an alyzed genetic polymorphism and allelic Variation of the HLA-DOA gene in 37 HLA class II homozygous typing cells using the direct DNA sequencing techn ique. As a result, we recognized at least eight allelic variations, DOA*010 11, *0101201, *0101202, *0101203, *01013, "0101401, *0101402 and *01015. No ne of them, however, result in amino acid substitution. The HLA-DOA gene ha s been identified in other mammals as well, and the nucleotide sequences we re well conserved among these species. These results suggest that the DOA m olecule has undergone strong selective pressure to preserve functional stru cture and conformation required for interaction with the DM molecule, preve nting non-synonymous amino acid substitution.