Serological and structural analysis of HLA class I molecules: beta 2-microglobulin interacts with the two external domains of the HLA class I heavy chain.
The serological reactivities of HLA class I molecules were studied in relation to structural modifications of these molecules, including shuffling of external exons and exchange of human beta 2-microglobulin for beta 2-microglobulin from different species. Two major clusters (I and II) of monomorphic and polymorphic antigenic determinants could be delineated. beta 2-Microglobulin participates in the formation of the two clusters, indicating that the light chain interacts tightly with the two external domains of the HLA class I heavy chain. However, external molecules can modify these interactions and alter the antigenic structure of the overall molecule. Thus, fixation on HLA class I molecules of the Fab fragment of a monoclonal antibody directed at antigenic determinants associated with cluster II resulted in enhanced fixation of a monoclonal antibody (B10.6) related to cluster I. The structural and functional implications of these results are discussed.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000939:Epitopes; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D046911:Macromolecular Substances; D011110:Polymorphism, Genetic; D011485:Protein Binding; D011863:Radioimmunoassay; D001613:beta 2-Microglobulin / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006680:HLA Antigens; D046911:Macromolecular Substances; D001613:beta 2-Microglobulin