Specificity of T-cell clones illustrates altered self hypothesis

Abstract

Cytotoxic T lymphocytes (CTLs) recognize foreign antigens in the context of self major histocompatibility antigens. In the mouse this phenomenon is called H–2 restriction as H–2 is the major histocompatibility complex. Two theories have been proposed to explain the dual requirement for CTLs to kill specifically target cells: (1) the two-receptor hypothesis proposes that T cells have an anti-self H–2 receptor and a distinct anti-foreign (anti-X) receptor^1,2; (2) the altered self hypothesis proposes that T cells recognize complex antigens or interaction antigens created by the physical interaction of self H–2 molecules and X in the target cell membrane^3,4. Here we report the isolation of CTL clones which recognize H–2^k-plus-X and cross-react with H–2^d-plus-Y. Because the clones recognize two pairs of antigens and not any combination, for example, H–2^k-plus-Y, they support very strongly the principle of altered self recognition, that is, that only the complex of H–2 and foreign antigen is recognized and not either component independently.