Functional reprogramming of the primary immune response by T cell receptor antagonism.
The T cell receptor must translate modest, quantitative differences in ligand binding kinetics into the qualitatively distinct signals used to determine cell fate. Here, we use mice that express an endogenous T cell receptor (TCR) antagonist and an adoptive transfer system to examine the influence of TCR signal quality on the development of effector function. We show that activation of antigen-specific T cells in the presence of an antagonist results in a functional reprogramming of the primary immune response, marked by altered T cell homing, a failure to develop effector function, and ultimately clonal elimination by apoptosis. Importantly, antagonism does not block cell division, implying that the signals promoting clonal expansion and effector differentiation are distinct.
Haribhai
Dipica
D
Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
Edwards
Brandon
B
Williams
Mary L
ML
Williams
Calvin B
CB
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D017637:Clonal Deletion; D004789:Enzyme Activation; D007108:Immune Tolerance; D007114:Immunization; D007156:Immunologic Memory; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008806:Mice, Inbred AKR; D008822:Mice, Transgenic; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D053148:Caspase 3; D020169:Caspases; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C054979:antigen T cell receptor, zeta chain; C509248:Ptpn6 protein, mouse; C505409:Casp3 protein, mouse