Previous studies have shown that tolerogenic anti-CD4 (W3/25) and anti
-LFA-1 mAb (LRTC1) which block T cell activation paradoxically enhance
T cell-mediated antigen presentation. Lasting T cell APC (T-APC) acti
vity requires an initial exposure of T cells to these mAb in the prese
nce of professional APC and antigen. This study revealed a central mec
hanism regulating the duration of T-APC activity. T cell recognition o
f class II MHC complexes on T-APC catalyzed a rapid decay in the prese
ntation of agonistic antigens, whereas partial agonistic signals decay
ed at a slower rate. Likewise, blockade of agonistic T-T cell autoreco
gnition by these mAb led to the persistence of agonistic MHC/antigen o
n T-APC. The best predictor of T-APC activity was related to the abili
ty of clonal T cells to respond to antigen presented by neighboring T
cells. Strong responders were inefficient T-APC, whereas inefficient r
esponders were strong T-APC. Addition of irradiated myelin basic prote
in (MBP)-specific responders to T-APC cultures specifically inhibited
the subsequent presentation of MBP but not conalbumin, and vice versa.
T-APC presentation of antigen to responder T cells also resulted in r
educed surface expression of class II MHC I-A glycoproteins on T-APC.
These findings indicate that agonistic recognition of antigen on T-APC
specifically inhibits subsequent presentation of that antigen, wherea
s antagonistic MHC/antigen complexes are preserved for an enduringT-AP
C activity. (C) 1998 Academic Press.