PARTIAL AGONISM ELICITS AN ENDURING PHASE OF T-CELL-MEDIATED ANTIGEN PRESENTATION

Previous studies have shown that the anti-CD4 mAb W3/25 strongly enhan ces T cell APC (T-APC) activity. In this study, single positive CD4(+) and double negative (DN) (CD4(-)CD8(-)) T-helper cells specific for t he 55-69 or 72-86 sequence of guinea pig (GP) myelin basic protein (GP EMBP) were used to study CD4 regulation of T-APC activity. Clones were cultured with irradiated SPL and GPMBP or rat (R) MBP for 2-3 days, w ere propagated in IL-2 for another 1-3 days, were irradiated, and were used as T-APC. DN T cells specific for GP55-69 effectively presented GPMBP and were superior APC compared to other CD4(+) T cells for prese ntation of this antigen, In contrast, DN T cells specific for the domi nant encephalitogenic 72-86 determinant did not effectively present th e agonist GPMBP but potently presented the partial agonist RMBP. The h eightened APC activity of DN T cells reflected the lack of CD4 because the anti-CD4 mAb W3/25 promoted T-APC activity of CD4(+) T cells to t hose levels expressed by DN T cells, Overall, T cells with potent reac tivity to GPMBP or RMBP were subsequently unable to present that antig en, whereas T cells exhibiting partial or low antigen reactivities wer e highly effective APC for presentation of that antigen. The unrelated antigen conalbumin was presented by MBP-specific clones only when add ed to culture with a specific partial agonist. Together, these data in dicate that partially agonistic MHC ligands promote prolonged expressi on of T-APC activity and that DN T cells may be specialized to mediate postactivational antigen presentation. (C) 1998 Academic Press.