Recognition of H–2 domains by cytotoxic T lymphocytes

Abstract

The polymorphic major histocompatiblity antigens (H–2) have a crucial role in the activation of antigen-specific T lymphocytes. Thus, H–2 antigens are not only recognized by allogeneic lymphocytes leading to generation of cytotoxic T lymphocytes (CTLs), but it has also been demonstrated that in syngeneic systems most T cells are only able to recognize foreign antigens in conjunction with their own MHC (major histocompatibility complex) antigens. This phenomenon, termed H–2 restriction¹, may be the key to our understanding of the biological function of MHC antigens. It is not clear whether recognition by T cells of H–2 on a molecular level is confined to particular domains on the H–2 molecule, nor whether the same polymorphic H–2 sites, which are characterized by antibodies, are recognized by allogeneic as well as by H–2-restricted syngeneic CTLs. Previous findings² indicate the existence of at least two major polymorphic domains on the H–2K^k molecule as defined by antibodies. Here we show the existence of CTLs with specifity for these polymorphic domains, and the preferential recognition of a particular domain by both alloreactive as well as H–2-restricted CTLs.