Differential requirements for class II MHC antigen in human T cell activation.
We have employed three different models of major histocompatibility complex (MHC) antigen to investigate the role of these antigens in some aspects of human T cell activation in in vitro; specifically the induction of lymphokine synthesis and receptors, and in antigen presentation. Those models were (1) allogeneic platelets (class I alone); (2) D/DR compatible lymphocytes (class I plus nonimmunogenic class II); and (3) allogeneic heat-treated lymphocytes. After heating at 45 C for 1 hr, the latter are completely viable and express both class I (HLA A and B) and class II (HLA, DR, MT/MB) MHC antigens but do not stimulate in the mixed lymphocyte reaction (MLR). These models were compared with conventional irradiated MLR stimulating or antigen-presenting cells. Only the conventional cells were able to stimulate the synthesis of interleukin-1 and interleukin-2. Also, irradiated but not heat-treated non-T cells could present soluble antigen to autologous T cells. This implies that intact and unmodified Ia molecules are required for those responses. On the other hand, heat treated allogeneic lymphocytes and D/DR-compatible lymphocytes but not allogeneic platelets could induce responsiveness to interleukin-2. This function appears to require a heat stable but nonallogeneic component of the class II molecules. Our previous observations employing these models have also shown that there is yet a third category of T cell responses, including memory cell priming and suppressor cell induction, that can occur in the presence of predominantly class I antigen. Taken together, these data illustrate the functional heterogeneity of T cell responses to Ia-like antigens. The possible relevance of these findings to clinical transplantation is discussed.
D000938:Antigen-Presenting Cells / Q000276:immunology; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008211:Lymphocyte Cooperation; D008222:Lymphokines / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D008222:Lymphokines; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2