Product of a transferred H-2Ld gene acts as restriction element for LCMV-specific killer T cells

Anders Örn, Robert S. Goodenow, Leroy Hood, Peter R. Brayton, Jerold G. Woodward, Richard C. Harmon, Jeffrey A. Frelinger

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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 responses1,2. 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-2d haplotype and their class I molecules are denoted Kd, DD 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 activated5,6. 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-2k haplotype and monoclonal antibodies can be used to distinguish H-2d molecules from the endogenous H-2 k products. Recently, we have demonstrated that both Ld (ref. 8) and Kd molecules (unpublished data) expressed on transformed L cells can act as target antigens for alloreactive cytotoxic T lymphocytes. Here we show that the Ld molecule on transformed mouse L cells can serve as a restricting element in lymphocytic choriomeningiris virus (LCMV) infection, whereas its Kd counterpart cannot.

Original languageEnglish (US)
Pages (from-to)415-417
Number of pages3
JournalNature
Volume297
Issue number5865
DOIs
StatePublished - Dec 1 1982
Externally publishedYes

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    Örn, A., Goodenow, R. S., Hood, L., Brayton, P. R., Woodward, J. G., Harmon, R. C., & Frelinger, J. A. (1982). Product of a transferred H-2Ld gene acts as restriction element for LCMV-specific killer T cells. Nature, 297(5865), 415-417. https://doi.org/10.1038/297415a0