The role of three distinct Ia-like antigen molecules in human T cell proliferative responses: effect of monoclonal anti-Ia-like antibodies.

Murine monoclonal antibodies (MoAb) to three distinct Ia-like molecules were studied for their inhibitory effects on antigen- and alloantigen-induced T cell proliferations. The MoAb were classified into three groups according to the molecules they recognized. Both the group I MoAb reacting with DR molecules and the group III MoAb were capable of inhibiting T cell proliferative responses to PPD- and HSV-Ag-pulsed APC, autologous B-LCL, and alloantigens. On th other hand, the group II MoAb, which reacted with a determinant on the molecule carrying MB1 determinants, was only capable of inhibiting T cell responses to alloantigens. These results suggest that the structure of the molecules correlates with the functional repertoire of the human Ia-like antigens.

Both HLA-DR restricted and nonrestricted functions of adherent cells are required for induction of T lymphocyte proliferative responses.

There appeared to be two distinct functions of adherent cells in human T lymphocyte proliferative responses to purified protein derivative (PPD). The first is antigen-presenting ability which is mediated by antigen-presenting cells (APC) among adherent cells. By employing antiserum blocking pretreatment of APC, it was revealed that HLA-DR antigens are involved in this function and that identity or partial identity of HLA-DR antigens between APC and T lymphocytes is required for T lymphocyte antigen recognition. The second function is mediated by the soluble factor produced by adherent cells and is HLA-DR nonrestricted. Although it remains unclear whether APC and adherent cells producing the soluble factor belong to the same cell population, this second function might lead T lymphocytes to proliferative as long as T lymphocytes recognize antigen (PPD) via APC.

Human antigen-presenting cells: characterization of the cells in the T-lymphocytes proliferative response.

Human antigen-presenting cells (APC) which present the antigen to T lymphocytes resulting in a T-lymphocyte proliferative response were found among peripheral mononuclear cells (MNC), by employing purified protein derivative (PPD) as soluble antigen. To assess the adherence capacity of human antigen-presenting cells, MNC were separated by plastic Petri dishes or nylon wool columns. Plastic nonadherent cells were almost equivalent to unseparated cells in antigen-presenting ability. Plastic adherent cells, however, showed better antigen-presenting ability than unseparated cells. On the other hand, cells passed over nylon wool columns showed essentially no ability to present PPD to T lymphocytes. Removal of phagocytic cells by carbonyl iron resulted in about 50-70% reduction in antigen-presenting ability. Carrageenan, which is known to be toxic to macrophages, had no effect on APC. By using both rabbit anti-human Ia-like antiserum and alloantiserum specific for HLA-DR phenotype and complement, it was shown that APC possessed Ia-like antigens, whereas they did not bear surface immunoglobulins. These results indicate that the human APC is probably a cell in the monocyte-macrophage lineage. Allogeneic MNC were used as APC in order to determine whether any genetic restriction exists between MNC as APC and responding T lymphocytes. Optimal stimulation was shown to require identity of mixed leukocyte reaction (MLR)- activating determinants between APC and T lymphocytes. It is however, obscure whether an HLA-D region restriction exists in these combinations because PPD-pulsed allogeneic MNC lost their ability to elicit even MLR. It is possible that this failure to elicit MLR was caused by T lymphocytes among the MNC used as APC.