MHC-Restricted Antibodies: Facts and Interpretation
T cell recognition of foreign antigen is MHC restricted. This restriction holds for helper as well as cytolytic T cells. A major part of the problem of MHC restriction is connected with the structure and binding site specificity of the T cell receptor (TcR). The serendipity of discovery and changing views about TcR specificity have been reviewed by various authors. The most typical situation can still be characterized by the original description of the MHC restriction phenomenon by Zinkernagel and Doherty (1974, 1979). They found that antiviral cytotoxic T-lymphocytes (CTLs) recognize antigen only on target cells together with self-MHC molecules. The phenomenon has been amply confirmed, although various observations have extended the horizon: (a) viral-specific CTLs frequently recognize MHC alloantigens without virus, (b) determinants shared by various MHC molecules can restrict antigen recognition (cross-reactions among MHC molecules), (c) determinants shared by various foreign antigens can be recognized by the same CTL (cross-reactions among foreign antigens), (d) allo-(MHC)-restricted clones are induced when responder cells are stimulated with alloantigen and virus, and (e) exceptionally, autoreactive T cell clones have been described that have recognized not only allogeneic but also syngeneic cells without antigen.
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