Cited by 465T-cell and B-cell ImmunologyProtein Tyrosine PhosphatasesImmune Response and Inflammation

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TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways

Štefanová, Irena, Hemmer, Bernhard, Vergelli, Marco, Martin, Roland, Biddison, William E., Germain, Ronald N.·2003·Nature Immunology

DOI 10.1038/ni895

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Abstract

Functional discrimination between structurally similar self and foreign antigens is a main attribute of adaptive immunity. Here we describe two feedback mechanisms in T lymphocytes that together sharpen and amplify initial signaling differences related to the quality of T cell receptor (TCR) engagement. Weakly binding ligands predominantly trigger a negative feedback loop leading to rapid recruitment of the tyrosine phosphatase SHP-1, followed by receptor desensitization through inactivation of Lck kinase. In contrast, strongly binding ligands efficiently activate a positive feedback circuit involving Lck modification by ERK, preventing SHP-1 recruitment and allowing the long-lasting signaling necessary for gene activation. The characteristics of these pathways suggest that they constitute an important part of the mechanism allowing T cells to discriminate between self and foreign ligands.

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RETRACTED: Uncoupling IL-2 Signals that Regulate T Cell Proliferation, Survival, and Fas-Mediated Activation-Induced Cell Death
Parijs, L. V., Refaeli, Y., Lord, J. D., Nelson, B. H., Abbas, A. K., & Baltimore, D. (1999) · Immunity · doi:10.1016/s1074-7613(00)80103-x · Cited by 420
Retracted
RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement
Shinkai, Y. (1992) · Cell · doi:10.1016/0092-8674(92)90029-c · Cited by 2,651
SH2 domains recognize specific phosphopeptide sequences
Songyang, Z. (1993) · Cell · doi:10.1016/0092-8674(93)90404-e · Cited by 2,620
The Biochemical Basis of an All-or-None Cell Fate Switch in Xenopus Oocytes
Ferrell, J. E., & Machleder, E. M. (1998) · Science · doi:10.1126/science.280.5365.895 · Cited by 1,052
The Biochemistry and Cell Biology of Antigen Processing and Presentation
Germain, R. N., & Margulies, D. H. (1993) · Annual Review of Immunology · doi:10.1146/annurev.iy.11.040193.002155 · Cited by 1,003
Self-citation
The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice.
Seder, R. A., Paul, W. E., Davis, M. M., & Groth, B. F. D. S. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.4.1091 · Cited by 994
Kinetic proofreading in T-cell receptor signal transduction.
McKeithan, T. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.5042 · Cited by 964
IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression.
Ding, L., Linsley, P. S., Huang, L. Y., Germain, R. N., & Shevach, E. M. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.3.1224 · Cited by 829
Self-citation
Defective Thymocyte Maturation in p44 MAP Kinase (Erk 1) Knockout Mice
Pagès, G., Guérin, S., Grall, D., Bonino, F., Smith, A., Anjuere, F., Auberger, P., & Pouysségur, J. (1999) · Science · doi:10.1126/science.286.5443.1374 · Cited by 654
Receptor clustering as a cellular mechanism to control sensitivity
Bray, D., Levin, M. D., & Morton-Firth, C. J. (1998) · Nature · doi:10.1038/30018 · Cited by 613

Show all 63 references

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Authors: Štefanová, I., Hemmer, B., Vergelli, M., Martin, R., Biddison, W. E., & Germain, R. N.
Affiliations: National Institutes of Health (US)
Corresponding author: Germain, Ronald N.
ORCID: Hemmer, Bernhard
Germain, Ronald N.
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2003-02-10
Volume: 4
Issue: 3
Pages: 248-254
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni895
OpenAlex: W1971692004
Cited by: 465
References: 63
Citations by year: 2026: 8 · 2025: 10 · 2024: 15 · 2023: 13 · 2022: 14 · 2021: 19 · 2020: 19 · 2019: 19 · 2018: 11 · 2017: 16 · 2016: 17 · 2015: 14 · 2014: 28 · 2013: 24 · 2012: 28
FWCI: 7.67
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: T cell receptor signaling, ligand discrimination, Lck kinase, receptor desensitization, T cell activation, protein tyrosine phosphatase, signal amplification
MeSH terms: Animals, Humans, Ligands, Mice, Transgenic, Receptors, Antigen, T-Cell, Signal Transduction, Protein Tyrosine Phosphatases, CD8-Positive T-Lymphocytes, Mitogen-Activated Protein Kinases, Feedback, Physiological, Intracellular Signaling Peptides and Proteins, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 6

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TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways

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