Specific lysis of murine cells expressing HLA molecules by allospecific human and murine H‐2‐restricted anti‐HLA T killer lymphocytes

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Abstract
The lysis by human and murine anti‐HLA cytolytic T lymphocytes (CTL) of murine cells expressing class I HLA molecule after gene transfection has been studied using two different murine cells: LMTK− and P815‐HTR‐TK−. Weak but significant HLA‐A11‐specific lysis was found occasionally with human CTL on the HLA‐A11+ L cells. On the contrary, P815‐A11 or P815‐A2 cells were lysed strongly and specifically by HLA‐A11 or HLA‐A2‐specific human CTL. The T8+T4− phenotype of the effector cells was confirmed and the reaction was inhibited by anti‐HLA class I monoclonal antibodies. Despite their higher sensitivity to human CTL, the P815‐HLA+ cells did not express higher levels of HLA antigens than L cells, and the presence or the absence of human β2 microglobulin was irrelevant. Anti‐human LFA‐1 antibodies abrogated the lysis of P815‐A11+ cells showing that the LFA‐1 receptor which is apparently lacking on the L cell surface was on the contrary expressed on P815 cells. On the other hand, murine anti‐HLA CTL have been prepared by immunizing mice against syngeneic HLA‐A11+ L cells. They lysed very efficiently and specifically these cells, but appeared completely devoid of activity against human HLA‐A11 target cells. This barrier was apparently due to the H‐2 restriction of these H‐2k anti‐HLA murine CTL, as shown by their inability to lyse allogeneic H‐2d cells expressing HLA‐A11, and by the blocking of their activity by anti H‐2k antibodies. By contrast, xenogeneic anti‐HLA CTL obtained by immunizing murine lymphocytes against human cells lysed both human and murine HLA+ cells but they reacted with a monomorphic epitope of the HLA molecule in a nonrestricted way. These results show that (a) human cells lyse very efficiently P815 murine cells expressing HLA class I antigens; (b) the higher sensitivity of P815 cells compared to L cells is probably due to the presence of a LFA‐1 receptor on these cells; (c) a class I molecule of human origin can be seen as an H‐2‐restricted minor histocompatibility antigen in another species.

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