Abstract
PRODUCTS of the major histocompatibility complex (MHC) are important as target structures in T lymphocyte-mediated cytolysis. In mice, virus (or hapten)-sensitised T cells are cytotoxic for specific virus-infected (or hapten-modified) target cells exclusively when syngeneic or at least identical for either the K or D region of the MHC1–5. These findings led to the ‘altered-self’ hypothesis6 which assumed that cytotoxic T cells do not recognise specific viral antigens, but rather a modification of histocompatibility antigens induced by the viral infection. One prediction of this theory was that murine cells expressing viral antigens but lacking H–2 determinants would be resistant to T cell-mediated lysis. Indeed, this fact was established recently by Zinkernagel and Oldstone using murine F 9 teratoma cells7. There is still no evidence for the involvement of HLA antigens in the process of immune killing of virus-infected target cells by human T lymphocytes. But, Svedmyr and Jondal have shown that peripheral T cells from patients with infectious mononucleosis (IM)—and not from normal donors—killed specifically Epstein–Barr virus (EBV) genome-carrying B lymphoblastoid cell lines8 and Burkitt's lymphoma cells9. By contrast, these T cells were devoid of any cytotoxic activity against EBV negative cell lines. Similar data were obtained by other workers10,11. Thus, peripheral T cells from patients with infectious mononucleosis seemed to be sensitised to viral coded determinants, and could presumably be used in a model to study T-lymphocyte killing of virus-infected cells in human. If, in man as well as mouse, the MHC is directly involved in the target structure recognised by virus-sensitised cytolytic T lymphocytes, HLA-lacking target cells should be resistant to immune T-ceil killing. We report here that Daudi cells, originating from a human Burkitt's lymphoma line and lacking HLA products12–14, are resistant to lysis by EBV-sensitised peripheral T lymphocytes from patients with infectious mononucleosis.
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TURSZ, T., FRIDMAN, W., SENIK, A. et al. Human virus-infected target cells lacking HLA antigens resist specific T-lymphocyte cytolysis. Nature 269, 806–808 (1977). https://doi.org/10.1038/269806a0
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DOI: https://doi.org/10.1038/269806a0
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