Xenogeneic cytotoxic T-cell clones recognize alloantigenic determinants on HLA-A2

Long-term murine cytotoxic T-cell clones arising in response to stimulation with human lymphoblastoid cells and reactive with the HLA-A2 antigen are characterized. These clones distinguish between HLA-A2 and 21 other serologically defined HLA-A and -B antigens. In addition, most clones discriminate between prototypical HLA-A2 antigens, expressed by the majority of HLA-A2-positive individuals, and variant HLA-A2 antigens, which are serologically identical with the prototype, but distinguishable by human cytotoxic T cells and by biochemical analysis. This discrimination is reflected as an inability to cause any significant lysis of variant HLA-A2-expressing target cells at effector-to-target ratios 10- to 100-fold greater than those giving 50% lysis of prototype HLA-A2-expressing cells. By screening a panel of serologically HLA-A2-positive cells, a new variant HLA-A2-expressing cell line has been defined. The recognition patterns of these xenogeneic clones are suggested to reflect recognition of alloantigenic polymorphic determinants. Based on the strong bias in the xenogeneic T-cell repertoire for such determinants, we propose a model for T-cell recognition of class I products of the major histocompatibility complex.