The association of H-2Ld with human beta-2 microglobulin induces localized conformational changes in the alpha-1 and -2 superdomain.
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 cross-reactivity 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.
Nieto
M C
MC
Department of Cell and Molecular Biology, University of California, Berkeley 94720.
Song
E S
ES
McKinney
D
D
McMillan
M
M
Goodenow
R S
RS
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009038:Motion; D011485:Protein Binding; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D001613:beta 2-Microglobulin / Q000648:ultrastructure*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006183:H-2 Antigens; D001613:beta 2-Microglobulin