T cell anergy.
T cell clonal anergy is a proposed mechanism of immunologic self tolerance in which T cells become functionally inactivated after previous stimulation. MHC class II-restricted antigen presentation by different cell types has been speculated to have a role in determining activation vs. anergy in responding T cells. Human T cells express MHC class II after activation and have been shown to present high concentrations of degraded peptide antigen to autologous T cells resulting in clonal anergy. In contrast to low antigen dose T cell clonal anergy, which occurs in the absence of costimulation, T cell anergy induced by human T cell presentation of antigen results in both primary proliferation and secondary unresponsiveness to high-dose antigenic stimulation. Although clonal anergy was previously thought to prevent autoreactive T cells from ever responding to self antigen presented without costimulation, we postulate that T cell presentation of antigen represents a "fail-safe" mechanism of immunologic self tolerance that would anergize clonally expanded autoreactive T cells when they are surrounded by a high extracellular concentration of degraded self antigen.
LaSalle
J M
JM
Laboratory of Molecular Immunology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Hafler
D A
DA
D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II