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) activity requires and initial exposure of T cells to these mAb in the presence of professional APC and antigen. This study revealed a central mechanism regulating the duration of T-APC activity. T cell recognition of class II MHC complexes of T-APC catalyzed a rapid decay in the presentation of agonistic antigens, whereas partial agonistic signals decayed at a shower rate. Likewise, blockade of agonistic T-T cell autorecognition by these mAb led to the persistence of agonistic MHC/antigen on T-APC. The best predictor of T-APC activity was related to the ability of clonal T cells to respond to antigen presented by neighboring T cells. Strong responders were inefficient T-APC, whereas inefficient responders were strong T-APC. Addition of irradiated myelin basic protein (MBP0-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 reduced surface expression of class II MHC I-A glycoproteins on T-APC. These findings indicate that agonistic recognition of antigen of T-APC specifically inhibits subsequent presentation of that antigen, whereas antagonistic MHC/antigen complexes are preserved for an enduring T-APC activity.