Cytotoxic T lymphocytes induced against allogeneic I-region determinants react with ia molecules on trinitrophenyl-conjugated syngeneic target cells*

Data presented in this communication support the conclusions that CTL can recognize I-region determinants on TNP-modified syngeneic target cells and that a subset of the clones of CTL induced by allogeneic Ia antigens lyses targets bearing TNP-modified syngeneic Ia antigens. The clones of CTL induced by Ia antigen differences which lyse modified-self Ia antigen-bearing targets are distinct from those clones primarily directed at K- or D-coded determinants. Thus, varying the K or D alleles of either the stimulator or target cell does not significantly alter the lysis produced by I-region-specific CTL when tested on targets bearing allogeneic or modified syngeneic Ia antigens. Similarly, an antiserum directed at gene products of the H-2D locus does not reduce the target lysis by I-region-specific CTL. Only an antiserum specific for Ia determinants blocks lysis of CTL induced acrossI-region differences. When tested on modified syngeneic targets, an antiserum specific for syngeneic Ia specificities blocks the lysis of these targets by allogeneically induced CTL, while failing to inhibit the lysis of targets bearing the stimulating allogeneicI-region determinants. Added to the cold target data, these observations argue that there exists a significant subpopulation in the clones of CTL induced by allogeneic Ia determinants which recognize and lyse modified syngeneic Ia-bearing cells. These CTL, when presented with targets bearing modified K, I, and D determinants, recognize specifically the modified Ia antigen, though the K- and D-coded products are the major target antigens in most cytolytic systems (16). Important issues remain to be investigated concerning these I-region-directed clones of CTL. If, as we have suggested, they play an immunoregulatory role, the target of these T cells may be Ia-bearing cells involved in antigen presentation, in macrophage-T cell, T-T cell, or B-T cell interactions, or the factors comprised in part of complexed antigen and Ia determinants which seem to control cell-cell interactions in immune responses. The relationship between those Ia determinants which appear to be concerned with the regulation of the responses to thymus-dependent antigens and those which serve as targets for I-region-directed CTL also remains to be elucidated.