Crystallization and X-ray diffraction studies on the histocompatibility antigens HLA-A2 and HLA-A28 from human cell membranes.
The human histocompatibility antigens HLA-A and HLA-B are polymorphic cell surface glycoproteins encoded by the major histocompatibility complex. These molecules are the major targets for the immune response during tissue transplantation. They are recognized by cytolytic T-lymphocytes during the immune response against virally infected cells, and have been linked to variations in susceptibility to human autoaggressive and neoplastic diseases. To permit a description of the sites of interaction with alloantisera and T-cell receptors, we have begun a three-dimensional structure determination of HLA-A. We report the isomorphous cyrstallization of two antigenic specificities of papain-solubilized HLA-A, A2 and A28. Isoelectric focusing indicates that the well-ordered crystals incorporate the sialic acid microheterogeneity of the oligosaccharides. Crystallographic evidence indicates that the HLA-A molecule has an approximate 2-fold rotational symmetry axis which, combined with biochemical data, suggests that the domains of the molecule are paired alpha 1 to alpha 2 and alpha 3 to beta 2-microglobulin. This domain organization is similar to the arrangement of domains in the Fab and Fc fragments of immunoglobulins.
D002462:Cell Membrane; D003460:Crystallization; D006680:HLA Antigens; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D006801:Humans; D008954:Models, Biological; D014961:X-Ray Diffraction
D006680:HLA Antigens; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; C037164:HLA-A28 antigen