CLASS-II MHC PEPTIDE COMPLEXES ON T-CELL ANTIGEN-PRESENTING CELLS - AGONISTIC ANTIGEN RECOGNITION INHIBITS SUBSEQUENT ANTIGEN PRESENTATION/

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.