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  • Title: Cross-recognition of a mouse H-2-peptide complex by human HLA-restricted cytotoxic T cells.
    Author: Murray RJ, Brooks JM, Rickinson AB, Rowe M.
    Journal: Eur J Immunol; 1990 Mar; 20(3):659-64. PubMed ID: 1690661.
    Abstract:
    Epstein-Barr virus (EBV)-specific human cytotoxic T lymphocyte (CTL) lines from a virus-immune HLA-A11+ donor CMc produced significant lysis of transfected mouse P815 target cells (H-2d background) expressing an introduced HLA-A11 heavy chain gene and the EBV gene encoding latent membrane protein (LMP). To identify the target epitope being recognized, HLA-A11+ transfectants of P815/A11) were pre-exposed to synthetic peptides corresponding to fragments of the LMP sequence and the cells then tested for lysis by CMc effectors; untransfected P815 parent cells were included in these assays as control recipients of the same peptides. Unexpectedly, we identified a peptide preparation (corresponding to LMP residues 124-137) which specifically sensitized not only P815/A11 cells but also the parental P815 cells to lysis. Four independent anti-EBV CTL lines derived from donor CMc gave the same result and single-cell cloning confirmed that lysis was mediated by a subset of the HLA-A11-restricted EBV-specific CTL clones which dominate CMc effector populations. Two lines of evidence indicated that peptide presentation to the human CTL was occurring through H-2Kd molecules on the surface of P815/A11 and P815 cells: (a) a monoclonal antibody reactive with H-2Kd specifically blocked the lysis of both P815/A11 and P815 peptide-treated targets, and (b) on an extended target cell panel, peptide-mediated sensitization was also obtained with a second H-2d mouse line A20.2J and with an H-2Kd transfectant of the H-2k line R1E. This work has therefore identified EBV-specific HLA-A11-restricted human CTL which show fortuitous cross-recognition of a synthetic peptide in the context of a mouse H-2Kd molecule. Such potential for xenogeneic cross-reactivity needs to be borne in mind in situations where the target specificity of human CTL is being analyzed on HLA gene-transfected murine target lines.
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