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Association of β2-microglobulin with the α3 domain of H-2Db heavy chain

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Abstract

MHC class I molecules are heterotrimeric complexes composed of heavy chain, β2-microglobulin (β2m) and short peptide. This trimeric complex is generated in the endoplasmic reticulum (ER), where a peptide loading complex (PLC) facilitates transport from the cytosol and binding of the peptide to the preassembled ER resident heavy chain/β2m dimers. Association of mouse MHC class I heavy chain with β2m is characterized by allelic differences in the number and/or positions of amino acid interactions. It is unclear, however, whether all alleles follow common binding patterns with minimal contributions by allele-specific contacts, or whether essential contacts with β2m are different for each allele. While searching for the PLC binding site in the α3 domain of the mouse MHC class I molecule H-2Db, we unexpectedly discovered a site critical for binding mouse, but not human, β2m. Interestingly, amino acids in the corresponding region of another MHC class I heavy chain allele do not make contacts with the mouse β2m. Thus, there are allelic differences in the modes of binding of β2m to the heavy chain of MHC class I.

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Acknowledgements

We thank John Hirst for FACS analysis and Ted Hansen for providing the anti-mouse β2m antibody. This work was supported by the NIH grants AI48837 and AI41573 to S.V., and NCI core support grant 5P30 CA16087.

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  1. Mirjana Lilić

    Present address: Laboratory of Structural Microbiology, The Rockefeller University, 1230 York Avenue, RU Box 52, New York, NY 10021, USA

Authors and Affiliations

  1. Michael Heidelberger Division of Immunology, Department of Pathology and NYU Cancer Center, NYU School of Medicine, New York, NY 10016, USA

    Mirjana Lilić, Zoran Popmihajlov & Stanislav Vukmanović

  2. Department of Molecular Genetics, Howard Hughes Medical Institute, University of Cincinnati, Cincinnati, OH 45267, USA

    John J. Monaco

  3. Center for Cancer and Immunology Research, Children’s Research Institute, Children’s National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010-2970, USA

    Stanislav Vukmanović

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  1. Mirjana Lilić
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Correspondence to Stanislav Vukmanović.

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Lilić, M., Popmihajlov, Z., Monaco, J.J. et al. Association of β2-microglobulin with the α3 domain of H-2Db heavy chain. Immunogenetics 55, 740–747 (2004). https://doi.org/10.1007/s00251-003-0639-9

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  • DOI: https://doi.org/10.1007/s00251-003-0639-9

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