INHIBITION OF KILLER-TARGET CELL-INTERACTION BY MONOCLONAL ANTI-H-2 ANTIBODIES

The sites on target cells with which cytotoxic T lymphocytes interact were characterized using three different monoclonal BALB/c anti‐CBA antibodies derived from plasma cell hybrids. The antibodies all reacted with H‐2Kk and appeared to recognize public specificities H‐2.5,11 and 25, respectively. Allogeneic killing directed at products of H‐2Kk was inhibited by all three antibodies, irrespective of the H‐2 haplotype of the responder; cytotoxicity directed at products of another allele, H‐2Kd, or of the H‐2 D region on the same target cell was not affected. The antibodies did not inhibit killer cells carrying H‐2Kk. Cytotoxic reactions against minor histocompatibility antigens, including the male‐specific antigen H‐Y, were also blocked by all three monoclonal antibodies when restricted by H‐2Kk, but not when restricted by H‐2D on the same target cell. Cytotoxic T lymphocytes thus appear to interact with their target via the same, serologically defined H‐2Kk molecule which carries public specificities, whether they recognize it as an alloantigen or as self. This argues against the existence of separate H‐2 K‐encoded molecules recognized by killer cells only and against H‐2 specific modifications of minor histocompatibility antigens as the basis of H‐2 restriction. One of the antibodies, 27 R9, which reacted with H‐2Kk and H‐2′ and was thought to recognize specificity H‐2.25, showed a weak cytotoxic reaction but bound with a high titer to H‐2 Dk, a reaction that has not previously been described. This antibody selectively and with a very high titer inhibited male‐specific cytotoxicity restricted by H‐2Dk, but did not significantly interfere with allogeneic killing against products of the H‐2 Dk region nor apparently with H‐2Dk‐ restricted cytotoxicity specific for other minor antigens. The results suggest the existence of at least two different restriction elements controlled by the H‐2Dk region. Copyright © 1979 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim