Interaction between MHC-encoded products and cloned T cells. II. Analyses of physiological requirements indicate two different pathways of stimulation by class I alloantigens.

The interaction between class I major histocompatibility complex (MHC) products and T cells was studied using H-2Kb-specific alloreactive T-cell lines and clones obtained by repeated in vitro stimulation with allogeneic cells. Induction of proliferation of these T cells appeared to involve two signals: the H-2Kb alloantigen and interleukins. Immunopurified liposome-inserted H-2Kb, which stimulates specific secondary in vitro cytotoxic T lymphocyte (CTL) responses, could not replace cell-associated H-2Kb in the stimulation of these T-cell lines, even in the presence of feeder cells and interleukins. When T-cell lines were initiated in vitro and repeatedly stimulated with H-2Kb liposomes and feeder cells, it was possible to obtain T cells that could proliferate in response to H-2Kb liposomes in the presence of feeder cells and interleukin-2-containing supernatants or on H-2Kb-expressing cells. Only stimulation with cells permitted maintenance of these T cells in culture for more than 12 weeks. Analyses of cell surface markers and of patterns of inhibition of proliferation by monoclonal antibodies (mAb) of T-cell lines induced in vitro with cell- or liposome-associated H-2Kb indicated that T-cell stimulation by class I antigen can occur in at least two ways. In the first, the H-2Kb-induced proliferation of Lyt-1- Lyt-2+ T4- T cells is inhibited by H-2Kb- and by Lyt-2-specific mAb, but not by Ia or T4-specific mAb. In the second, both Lyt-2+ and T4+ T cells are involved and the H-2Kb-induced proliferation is inhibited by H-2Kb- and Lyt-2-specific mAb and by Ia- and T4-specific mAb.