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PMID: 11904393 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dissociation of peripheral T cell responses from thymocyte negative selection by weak agonists supports a spare receptor model of T cell activation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 7 ·2002-04-02 ·Pages 4520-5

McNeil LK, Evavold BD

Abstract

We have focused on stability of the peptide-MHC complex as a determining factor of ligand potency for thymocytes and peripheral CD4+ T cell responses. MHC variant peptides that have low affinities and fast dissociation rates are different in that they stimulate proliferation and cytolysis of mature T cells (classifying the variant peptides as weak agonists) but do not induce thymocyte negative selection. The MHC variant weak agonists require significant receptor reserve, because decreasing the level of T cell receptor on mature T cells blocks the proliferative response. These results demonstrate that peripheral T cells are more sensitive to MHC variant ligands by virtue of increased T cell receptor expression; in addition, the data support a T cell model of the spare receptor theory.

MeSH Terms
Animals CD4-Positive T-Lymphocytes/immunology Female Histocompatibility Antigens/metabolism Ligands Lymphocyte Activation Male Mice Mice, Transgenic Models, Immunological Peptides/metabolism Receptors, Antigen, T-Cell/physiology
Chemicals
Histocompatibility Antigens Ligands Peptides Receptors, Antigen, T-Cell
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
McNeil Lisa K
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Evavold Brian D
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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
0027-8424
DOI
10.1073/pnas.072673899
Published
2002-04-02
Epub
2002-00-19
Pages
4520-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC123680
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.072673899 PMC Full Text View journal details
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