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

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Abstract

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 α-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 α1α2 or α3-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 °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.

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Acknowledgements

We thank Iwona Stroynowski, Attila Kumánovics, and Toyoyuki Takada for helpful discussions, Tiencia Dupass for technical assistance, and Olga Zagnitko, Teresa Bannister and Clive Slaughter of the Howard Hughes Biopolymer Facility for DNA sequencing. This work was supported in part by NIH grant AI 37818.

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Author notes

  1. Yuki F. Moore

    Present address: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA

    Yuki F. Moore & Kirsten Fischer Lindahl

  2. Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA

    Yuki F. Moore, Doris Lambracht-Washington, Piotr Tabaczewski & Kirsten Fischer Lindahl

  3. Transplantationslabor, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany

    Doris Lambracht-Washington

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  1. Yuki F. Moore
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Corresponding author

Correspondence to Kirsten Fischer Lindahl.

Additional information

The nucleotide sequences reported in this paper have been submitted to GenBank with the accession numbers AY302188–AY302217 for all H2-M2 sequences and AY302218 for RT1.M2, AY326271 for RT1.M2-2, and AY327254 for the RT1.M2 microsatellite marker

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Moore, Y.F., Lambracht-Washington, D., Tabaczewski, P. et al. Murine MHC class Ib gene, H2-M2, encodes a conserved surface-expressed glycoprotein. Immunogenetics 56, 1–11 (2004). https://doi.org/10.1007/s00251-004-0661-6

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  • DOI: https://doi.org/10.1007/s00251-004-0661-6

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