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The Journal of Immunology, 2003, 170: 1224-1230.
Copyright © 2003 by The American Association of Immunologists

TCR Reserve: A Novel Principle of CD4 T Cell Activation by Weak Ligands 1

Lisa K. McNeil and Brian D. Evavold2

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322

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.


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