Partial Agonism Elicits an Enduring Phase of T-Cell-Mediated Antigen Presentation

Abstract

Previous studies have shown that the anti-CD4 mAbW3/25 strongly enhances T cell APC (T-APC) activity.In this study, single positive CD4+and double negative(DN) (CD4−CD8−) T-helper cells specific for the 55–69 or 72–86 sequence of guinea pig (GP) myelin basic protein (GPMBP) were used to study CD4 regulation ofT-APC activity. Clones were cultured with irradiatedSPL and GPMBP or rat (R) MBP for 2–3 days, were propagated in IL-2 for another 1-3 days, were irradiated, andwere 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 presentation of this antigen. In contrast, DN T cells specific for the dominantencephalitogenic 72–86 determinant did not effectively present the agonist GPMBP but potently presented thepartial agonist RMBP. The heightened APC activity ofDN T cells reflected the lack of CD4 because the anti-CD4 mAb W3/25 promoted T-APC activity of CD4+T cells to those levels expressed by DN T cells. Overall, T cells with potent reactivity to GPMBP or RMBP were subsequently unable to present that antigen, whereas T cells exhibiting partial or low antigen reactivities were highly effective APC for presentation of that antigen. The unrelated antigen conalbumin was presented by MBP-specific clones only when added to culture with a specific partial agonist. Together, these data indicate that partially agonistic MHC ligands promote prolonged expression of T-APC activity and that DN T cells may be specialized to mediate postactivational antigen presentation.