Selective modification of a private I-A allo-stimulating determinant(s) upon association of antigen with an antigen-presenting cell.

A large panel of alloreactive, interleukin 2 (IL-2)-producing T cell hybridomas was constructed from B10 alpha BALB/c primary mixed lymphocyte cultures (MLC). Functional hybrids had specificity for either I-Ad or I-Ed. These cells were used to probe determinants on Ia molecules in an attempt to detect molecular association between a nominal antigen and an Ia molecule on an antigen-presenting cell (APC). The response of a small number of these clones was significantly blocked by the addition of the Ir gene-controlled copolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) to culture. A comparison of the inhibited and uninhibited hybrids revealed an identical dose response curve. Further, both types of hybrids were activated by the same stimulator cell and frequently recognized the identical Ia molecule on that cell. Nevertheless, the inhibitory effect of GAT was localized to the stimulator cell and not to the T cell hybrids. All of the hybrids whose stimulation was blocked had specificity for the I-A molecule, which is the gene product known to control and restrict responsiveness to GAT. Further, only GT, but not a number of other related antigens, was also specifically inhibitory, which correlates with the known associational specificity of these antigens on an APC. Finally, the same stimulator cell could be shown to coordinately lose an allostimulatory determinant(s), while it was gaining an I-Ad plus GAT determinant(s). The implications of these findings on the nature of antigen-Ia association and on the role of polymorphic Ia determinants are discussed.

The same human alloreactive T cell clone can help both B lymphocytes and specific cytotoxic precursors.

Human alloreactive proliferating T cell clones have been compared for their capacity to provide help for B cell activation and the generation of a specific cytotoxic response. The results demonstrate that, when triggered by the relevant alloantigen, the same T cell clone can induce a strong polyclonal B cell activation and serve as the only source of helper cells for the generation of a specific cytotoxic response by any source of CTL precursors against any stimulator cell present in culture.

Enhancement of t lymphocyte functions by Fc fragments of immunoglobulins. I. Augmentation of allogeneic mixed lymphocyte culture reactions requires I-A- or I-B-subregion differences between effector and stimulator cell populations

Fc fragments derived from human Ig were found to be capable of enhancing T cell-mediated, antigen-induced proliferative and mixed lymphocyte culture responses. Maximum enhancement occurred when suboptimal amounts of antigen or suboptimal numbers of stimulator cells were employed. Augmentation of the allogeneic mixed lymphocyte culture reaction requires an I-A and/or I-B subregion difference between effector and stimulator cell populations. Although a significant proliferative response was observed with K- or D- region differences, Fc fragments were unable to enhance the response. The T cell population acted upon by Fc fragments in the potentiation of these responses bears the Lyt-1(+)23(-) phenotype.

Comparison of In Vitro Lymphocyte Proliferations Induced by Cytomegalovirus-Infected Human Fibroblasts and Cell-Free Cytomegalovirus

In vitro lymphocyte reactivity (LR) to cytomegalovirus (CMV)-infected human fetal fibroblasts (CMVFF) and cell-free CMV were measured by using lymphocytes from healthy donors. Lymphocytes from all seropositive donors were stimulated by CMVFF, whereas lymphocytes from negative donors were not. The optimal stimulator cell-to-lymphocyte ratio was in the range of 1:5 to 1:50, dependent on the virus dose used. LR to cell-free CMV was positive for 15 out of 18 seropositive donors and negative for 14 out of 16 seronegative donors. In most cases LR to CMVFF was considerably higher than LR to cell-free CMV. Within the CMV seropositive group there was no significant correlation between the LR to either CMVFF or cell-free CMV and the levels of antibodies to CMV early antigens or CMV late antigens. There was no strict correlation between LR to CMVFF and to cell-free CMV, especially not in tests with lymphocytes from two patients with CMV mononucleosis. Our data suggest that CMVFF and cell-free CMV are recognized (partly) by different subpopulations of CMV-specific memory lymphocytes. We conclude that the use of CMV-infected cells, in addition to cell-free CMV, in LR tests gives more reproducible and possibly also additional information about CMV-specific cellular immunity.