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PMID: 22223661 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 109 ·No. 3 ·2012-01-17 ·Pages 881-6

Gottschalk RA, Hathorn MM, Beuneu H, Corse E, Dustin ML, Altan-Bonnet G, Allison JP

Abstract

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.

MeSH Terms
Animals Cell Communication/drug effects Cell Proliferation/drug effects Dendritic Cells/cytology,drug effects,immunology Gene Expression Regulation/drug effects Histocompatibility Antigens/immunology Interleukin-2/pharmacology Male Mice Peptides/immunology Receptors, Antigen, T-Cell/immunology Receptors, Interleukin-2/immunology Signal Transduction/drug effects,immunology T-Lymphocytes/cytology,drug effects,immunology
Chemicals
Histocompatibility Antigens Interleukin-2 Peptides Receptors, Antigen, T-Cell Receptors, Interleukin-2
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gottschalk Rachel A
Department of Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Hathorn Matthew M
Beuneu Hélène
Corse Emily
Dustin Michael L
Altan-Bonnet Grégoire
Allison James P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1119763109
Published
2012-01-17
Epub
2012-00-05
Pages
881-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3271915
Subset
IM
Grants
NIAID NIH HHS · R01 AI083408 · United States
Howard Hughes Medical Institute · United States
NIAID NIH HHS · R01-AI083408 · United States
External Links
PubMed source DOI: 10.1073/pnas.1119763109 PMC Full Text View journal details
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