TCR reserve: a novel principle of CD4 T cell activation by weak ligands.
Some ligand-receptor systems have a receptor reserve where a maximal response can be achieved by occupation of a fraction of available receptors. An implication of a receptor reserve is the expansion of the number of ligands for response. To determine whether T cells follow receptor reserve, we have characterized the effect of reducing TCR levels on CD4 T cell responses elicited by altered peptide ligands that vary in potency. Agonist peptide is unaffected by a 90% reduction in TCR level while proliferation to weak agonists is significantly inhibited when TCR expression is reduced by 40%. Thymocyte-negative selection similarly demonstrates a differential requirement of TCR for response to agonist, weak agonist, and partial agonist. Therefore, our data demonstrate receptor reserve as a novel principle of T cell activation in which excess TCRs expand the antigenic repertoire to include less potent ligands.
McNeil
Lisa K
LK
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Evavold
Brian D
BD
D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D003574:Cytochrome c Group / Q000276:immunology / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D037181:Lectins, C-Type; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009036:Moths / Q000201:enzymology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D000099192:CD69 Antigens
D019138:Antibodies, Blocking; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003574:Cytochrome c Group; D006131:Growth Inhibitors; D007140:Immunoglobulin Fab Fragments; D037181:Lectins, C-Type; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000099192:CD69 Antigens