Product of a transferred H–2L^d gene acts as restriction element for LCMV-specific killer T cells

Abstract

The major histocompatibility complex (MHC) of the mouse, H–2 on chromosome 17, contains several families of genes encoding cell-surface molecules which have a role in mediating immune responses^1,2. The class I genes encode a family of homologous membrane proteins including the transplantation antigens K, D and L. These antigens reflect extensive genetic polymorphism which is apparent in the many different class I gene constellations or haplotypes found in mice (for example, BALB/c mice exhibit the H–2^d haplotype and their class I molecules are denoted K^d, D^D and L^d). Transplantation antigens serve as targets for T-cell killing in allogeneic immune responses such as in vivo graft rejection³ and destruction of allogeneic cells by cytotoxic T cells in vitro⁴. However, the physiological role of transplantation antigens may be to serve as restricting elements in virus-mediated T-cell killing of infected self cells. Virus infection of mice generates killer T cells whose receptors must interact with the foreign viral antigen and a class I molecule or restricting element for the cytotoxic effector function to be activated^5,6. Thus the T-cell receptor recognizes the viral antigen in the context of a class I molecule. To study the interaction between the T-cell receptor and the class I restricting element, we have used the mouse L-cell transformant 8–5 which expresses L^d molecules⁷ and the K7-65 transformant expressing K molecules (R.S.G. et al., in preparation). Mouse L cells are fibroblasts derived from C3H mice of H–2^k haplotype and monoclonal antibodies can be used to distinguish H–2^d molecules from the endogenous H–2^k products. Recently, we have demonstrated that both L^d (ref. 8) and K^d molecules (unpublished data) expressed on transformed L cells can act as target antigens for alloreactive cytotoxic T lymphocytes. Here we show that the L^d molecule on transformed mouse L cells can serve as a restricting element in lymphocytic choriomeningiris virus (LCMV) infection, whereas its K^d counterpart cannot.