Responsiveness of T cells to Mutant Major Histocompatibility Complex Class I Antigen.

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Abstract
Mechanisms of the activation of T cells responding to major histocompatibility complex (MHC) class I antigen were investigated with special reference lo interleukin 1 (IL‐1) production from stimulator‐type accessory cells. For this purpose, we used mainly fractionated Lyt‐2+ T cells of C57BL/6 (B6) mice as responder cells and irradiated spleen cells or those deprived of adherent cells of B6. C‐H‐2bm1 (bm 1) mice as stimulator ceils. Lyt‐2+ T cells of B6 mice proliferated in the presence of irradiated whole spleen cells of bm1 mice but did not to Sephadex G‐10 column‐passed bm1 spleen cells. The unresponsiveness in the latter case was overcome by the supplement of recombinant IL‐1 and/or IL‐2 in the culture medium. These interleukins were shown to promote the proliferative response of B6 Lyt‐2+ T cells in the presence of stimulator‐type for B cells. Both interleukins also facilitated the generation of cytotoxic T cells from BA Lyt‐2+ cells to H‐2Kbm1 antigen in the mixed lymphocyte culture deficient in stimulator‐type accessory cells. IL‐1 was shown to enhance the expression of IL‐2 receptor on the responding Lyt‐2+ T cells as assessed by flow cytometry. IL‐1 binding to responding T cells were also assayed by means of iodinated IL‐1 and was shown to increase significantly on responding Lyt‐2+ cells. Overall results indicate that accessory cells might play dual roles in the activation of Lyt‐2+ T cells responding to allogeneic MHC class 1 antigen: direct presentation of the antigen to responder T cells and production of IL‐1. Both signals are essentially required for Lyt‐2+ T cells responding to allogeneic MHC class I antigen to initiate proliferation and also to differentiate into cytotoxic T cells.

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