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The strength of T-cell receptor (TCR) stimulation and subsequent T-cell response depend on a combination of peptide-major histocompatibility complex (pMHC) density and potency. By comparing two different pMHC at doses yielding similar proliferation in vivo, we have highlighted unexpected differences in the qualitative and quantitative effects of TCR ligand. Measurements of cytokine sensitivity and two-photon imaging of T cell-dendritic cell (T-DC) interactions reveal discrimination between comparably weak stimuli resulting from either decreased pMHC potency or pMHC density. In addition, TCR-induced genes in broad gene expression profiles segregate into two groups: one that responds to cumulative TCR signal and another that responds to pMHC quality, independent of quantity. These observations suggest that models of TCR ligand discrimination must account for disparate sensitivity of downstream responses to specific influences of pMHC potency.

Original publication

DOI

10.1073/pnas.1119763109

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

05/01/2012

Volume

109

Pages

881 - 886

Addresses

Department of Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Keywords

Dendritic Cells, T-Lymphocytes, Animals, Mice, Peptides, Receptors, Antigen, T-Cell, Receptors, Interleukin-2, Interleukin-2, Histocompatibility Antigens, Cell Communication, Signal Transduction, Cell Proliferation, Gene Expression Regulation, Male