Murine MHC class Ib gene, H2-M2, encodes a conserved surface-expressed glycoprotein

• Published in: Immunogenetics (New York) 2004-04, Vol.56 (1), p.1-11
• Main Authors: Moore, Yuki F, Lambracht-Washington, Doris, Tabaczewski, Piotr, Fischer Lindahl, Kirsten
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Amino Acid Sequence; Amino acids; Animals; Base Sequence; Cloning, Molecular; Conserved Sequence; DNA, Complementary - genetics; Genes, MHC Class I; Haplotypes; HeLa Cells; Histocompatibility Antigens - genetics; Histocompatibility Antigens Class II - genetics; Humans; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Mice, Inbred Strains; Molecular Sequence Data; Phylogeny; Polymorphism, Genetic; Proteins; Rats; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Sequence Homology, Amino Acid; Transfection
• ISSN: 0093-7711; 1432-1211
• DOI: 10.1007/s00251-004-0661-6

We have determined the genomic sequence of H2-M2 in seven haplotypes from nine inbred strains of mice and in five wild-derived haplotypes. Except for the spretus haplotype sp1 with a premature stop codon, we found only limited polymorphism. Four of the five amino acid substitutions in the alpha-helices are at positions that would point out from the antigen-binding groove, indicating that the polymorphism might influence receptor recognition rather than antigen binding. The rat homologue, RT1.M2(lv1), has 89% identity to H2-M2 at the nucleotide level and 91% at the amino acid level, and it also encodes an intact MHC class I glycoprotein. Chimeric proteins with alpha(1)alpha(2) or alpha(3)-transmembrane domains encoded by H2-Q9 were detectable on the surface of transfectants with monoclonal antibodies against Qa2, and the full-length M2 protein, labeled by fusion with green fluorescent protein, was detectable with S19.8 monoclonal antibodies. The H2-M2 protein was thus expressed on the cell surface, even in TAP-deficient RMA-S cells at 37 degrees C, suggesting that it is TAP-independent. We conclude that H2-M2 is a conserved mouse class Ib gene that is translated to a surface-expressed MHC class I molecule with a function still to be elucidated.