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The association of H-2Ld with human beta-2 microglobulin induces localized conformational changes in the alpha-1 and- 2 superdomain

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Abstract

We have analyzed changes in the antigenicity of major histocompatibility complex class I molecules resulting from the association of human beta-2 micro-globulin (B2m) with the mouse class I heavy chain. In particular, the H-2Ld molecule exhibited enhanced crossreactivity for the 34-1-2 monoclonal antibody. In order to assess the nature of this structural alteration induced by human B2m, we utilized H-2 class I hybrid molecules in the mapping of the 34-1-2 determinant to the helical region of the alpha-1 domain. H-2Ld class I hybrid molecules were then used to establish the importance of the alpha-2 and- 3 domains in the observed increase of 34-1-2 cross-reactivity following exchange with human B2m. The H-2Ld hybrids suggest that alterations in interdomain contact are responsible for enhanced 34-1-2 cross-reactivity on the H-2Ld molecule. It is likely that this alteration arises through changes in class I conformation at regions of the molecule distant from points of contact between B2m and the class I molecule. This suggests that perturbations induced by association of human B2m with H-2Ld can affect the conformation of the alpha-1 and- 2 superdomain. That class I antigenic determinants are altered by the association of human B2m with mouse class I further suggests that the class I molecule is structurally flexible and may reflect the ability of the class I molecule to bind and present a vast array of disparate peptides to the T-cell receptor.

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Author notes

  1. Elizabeth S. Song

    Present address: Scripps Clinic and Research Foundation, 9203, La Jolla, CA, USA

Authors and Affiliations

  1. Department of Cell and Molecular Biology, Division of Immunology, 451 Life Science Annex, University of California, 94720, Berkeley, CA, USA

    Maria C. Nieto, Elizabeth S. Song & Robert S. Goodenow

  2. University of Southern California Medical Center, 90033, Los Angeles, CA

    Denise McKinney & Minnie McMillan

Authors
  1. Maria C. Nieto
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  2. Elizabeth S. Song
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  3. Denise McKinney
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  4. Minnie McMillan
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  5. Robert S. Goodenow
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Nieto, M.C., Song, E.S., McKinney, D. et al. The association of H-2Ld with human beta-2 microglobulin induces localized conformational changes in the alpha-1 and- 2 superdomain. Immunogenetics 30, 361–369 (1989). https://doi.org/10.1007/BF02425276

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  • DOI: https://doi.org/10.1007/BF02425276

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