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.