Individual differences in the cytotoxic T-lymphocyte response in man to public HLA determinants.

Abstract

The allospecific anti-HLA response of cytotoxic T lymphocytes (CTL) from 22 unrelated individuals and 7 monozygous twin pairs was examined. From each responder, CTL were generated in several responder-stimulator combinations, each mismatched for one HLA-A or -B antigen. The CTL were assayed in the cell-mediated lympholysis (CML) on panels of third-party target cells, comprising cells that express the stimulating antigen (specific target cells), cells that express an antigen cross-reactive with the stimulating antigen (CREG target cells), and cells that do not express either the stimulating or a cross-reactive antigen (nonsharing target cells). Individual variations in the allo-CTL response were observed. We identified individuals (responders) who showed a consistently narrow CTL response and those who showed a broad reaction pattern to various stimulator cells. The narrow response was restricted almost entirely to specific target cells; the broad response comprised lysis of specific, CREG, and nonsharing target cells. These differences were evidently not dependent on the HLA-A, -B, -C phenotype of the responder, because HLA-A, -B, (-C)-identical individuals responded differently to the same stimulator. The identical response of monozygous twins indicates that the allogeneic CTL response is genetically controlled. The CTL response is not regulated by the HLA-DR antigens of the responder, nor is it influenced by the DR mismatch between responder and stimulator. The observed differences were not dependent on sex or age and could not be explained by differences in the T-lymphocyte subsets (OKT3+, OKT4+, OKT8+) or by differences in proliferative reactivity to mitogens (phytohemagglutinin, concanavalin A, phorbol-myristate acetate, pokeweed mitogen, anti-T3 monoclonal antibodies). The IL-2 activity in the supernatants of mixed lymphocyte cultures of broad and narrow responder-stimulator combinations did not differ.