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Title
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Crystallization and X-ray diffraction studies on the histocompatibility antigens HLA-A2 and HLA-A28 from human cell membranes.
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Authors
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P.J.Bjorkman,
J.L.Strominger,
D.C.Wiley.
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Ref.
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J Mol Biol, 1985,
186,
205-210.
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PubMed id
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Abstract
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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.
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