Requirement of Ia-positive accessory cells in the MLR response against class II antigen on human B cell tumor line.

In this report we have made a comparative study of the capacity of normal human stimulator cells and Epstein-Barr virus-transformed human B cell line Wa (EBV-Wa) cells to stimulate alloreactive T cells. Class II antigen (presumably HLA-DR4 determinant) on EBV-Wa cells was shown to act as a stimulating molecule in the mixed lymphocyte reaction (MLR) through a blocking study by using anti-Ia antibodies. Furthermore, it was found that HLA-DR-positive accessory cells in the responder population were required to elicit MLR responses against HLA-DR antigen on EBV-Wa cells. In contrast, HLA-DR-positive accessory cells in the responding cell population were not essential for elicitation of MLR responses against HLA-DR antigen on normal allogeneic peripheral blood mononuclear cells, as reported. The cell-cell interaction between responder HLA-DR-positive accessory cells and responding T cells in a major histocompatibility complex (MHC)-restricted manner was required for eliciting MLR responses against class II antigen on EBV-Wa cells such as antigen-presenting cell-T cell interaction in soluble antigen-specific T cell proliferative responses. The function of HLA-DR-positive accessory cells in the responder population could not be substituted for by the presence of interleukin 1. Furthermore, there was no obvious correlation between the degree of surface HLA-DR antigen expression on EBV-Wa cells and its stimulating ability. Thus, two distinct types of allo-class II, antigen-specific T cell activation between normal human stimulator cells and EBV-Wa cells were shown to exist.