Evidence for an H–2/viral protein complex on the cell surface as the basis for the H–2 restriction of cytotoxicity

Abstract

CYTOTOXIC T lymphocytes generated in mice by immunisation with syngeneic Friend virus (FV)-induced tumour cells show H–2 restriction, that is, their cytotoxicity is specific not only for FV-associated antigenic determinants expressed on the surfaces of potential target cells but also for products of genes associated with the major histocompatibility complex, H–2 (ref. 1). We report here the results of studies concerning the role of molecules governed by genes in the K and D regions of the H–2 complex in the stimulation of FV-specific immune responses. Studies in other viral systems have shown that H–2-restricted T-cell killing can be associated with either K or D region determinants, that is, cytotoxic T cells from virus-infected mice will kill virus-infected target cells which share either the K or D region with the infected strain². Our studies, however, indicate that in the FV system there is a selective participation of H–2 determinants in virus-specific killing by cytotoxic T cells: BALB.B mice immunised with cultured, syngeneic FV-mduced tumour cells produce T cells with a cytotoxicity for other FV-induced tumour cells which depends only on identity at the H–2D (and not the H–2K) region of the H–2^b haplotype. This H–2D^b restriction in FV-specific cytotoxicity correlates with previous observations concerning: (1) partial co-capping of H–2D^b and not H–2K^b specificities following treatment with anti-FV antiserum³; (2) selective incorporation of H–2D^b and not H–2K^b specificities into mature FV particles⁴; and with our present observation of (3) blocking of T-cell cytotoxicity by anti-H–2D^b and not anti-H–2K^b antisera. We suggest that the basis for this correlation is the formation of H–2D^b/viral protein complexes on the surfaces of FV-infected cells, forming an ‘altered self’ molecule recognised by cytotoxic T cells as previously proposed for the mechanism of H–2 restriction⁵.