Y-antigen killing by T cells of women is restricted by HLA

Abstract

CYTOTOXIC T cells are important in graft rejection and in the control of virus infections, but the mode of interaction of these cells with their targets, particularly in man remains unclear. It has been shown in mice that products of genes in the major histocompatibility complex (H–2) are involved in these interactions even when the cytotoxic T cells are specific for viral or non-H–2 antigens. This involvement is seen as the requirements that the target cell must express the specific non-H–2 antigen and in addition the same H–2, D or K region antigens as were present on the cells which initiated the immune response^1–4. Cytotoxic T cells specific for viral or non-H–2 antigens are thus restricted in the targets that they can kill by the H–2 antigens on the targets. For example, cytotoxic T cells from H–2^b female mice suitably primed to the Y antigen of H–2^b males, will only kill cells from male mice carrying an H–2D region derived from H–2^b (refs 5,6). This report is to our knowledge the first clear demonstration that a similar restriction occurs in man. We describe a situation in man where cytotoxic reactions specific for non-HLA antigens can only occur when target cells carry both the HLA-A2 antigen of the original sensitising cell and the non-HLA target determinant(s). The strong association with maleness suggests that one of the specific antigens involved was coded for by the Y chromosome.