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.
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, USA.
M D
MD
Mannie
J P
JP
Nardella
G A
GA
White
P Y
PY
Arnold
D K
DK
Davidian
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D004676:Myelin Basic Protein; D010455:Peptides; D011948:Receptors, Antigen, T-Cell