| The receptor Ly108 functions as a SAP adaptor-dependent on-off switch for T cell help to B cells and NKT cell development. | |
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MedLine Citation:
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PMID: 22683125 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Humans and mice deficient in the adaptor protein SAP (Sh2d1a) have a major defect in humoral immunity, resulting from a lack of T cell help for B cells. The role of SAP in this process is incompletely understood. We found that deletion of receptor Ly108 (Slamf6) in CD4(+) T cells reversed the Sh2d1a(-/-) phenotype, eliminating the SAP requirement for germinal centers. This potent negative signaling by Ly108 required immunotyrosine switch motifs (ITSMs) and SHP-1 recruitment, resulting in high amounts of SHP-1 at the T cell:B cell synapse, limiting T cell:B cell adhesion. Ly108-negative signaling was important not only in CD4(+) T cells; we found that NKT cell differentiation was substantially restored in Slamf6(-/-)Sh2d1a(-/-) mice. The ability of SAP to regulate both positive and negative signals in T cells can explain the severity of SAP deficiency and highlights the importance of SAP and SHP-1 competition for Ly108 ITSM binding as a rheostat for the magnitude of T cell help to B cells. |
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Authors:
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Robin Kageyama; Jennifer L Cannons; Fang Zhao; Isharat Yusuf; Christopher Lao; Michela Locci; Pamela L Schwartzberg; Shane Crotty |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2012-06-07 |
Journal Detail:
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Title: Immunity Volume: 36 ISSN: 1097-4180 ISO Abbreviation: Immunity Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-07-03 Completed Date: 2012-09-13 Revised Date: 2013-06-11 |
Medline Journal Info:
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Nlm Unique ID: 9432918 Medline TA: Immunity Country: United States |
Other Details:
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Languages: eng Pagination: 986-1002 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, CA 92037, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Motifs Animals Antigens, Ly / genetics, physiology* B-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / immunology* Germinal Center / immunology Immunologic Deficiency Syndromes / genetics, immunology Immunological Synapses / immunology Intracellular Signaling Peptides and Proteins / deficiency, genetics, physiology Lymphocyte Cooperation / physiology* Lymphopoiesis / physiology* Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Natural Killer T-Cells / cytology* Phosphoric Monoester Hydrolases / physiology Phosphorylation Phosphotyrosine / physiology Protein Processing, Post-Translational |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI072543/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Ly; 0/Intracellular Signaling Peptides and Proteins; 0/Ly108 protein, mouse; 0/Sh2d1a protein, mouse; 21820-51-9/Phosphotyrosine; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC 3.1.3.56/inositol-1,4,5-trisphosphate 5-phosphatase |
| Comments/Corrections | |
Comment In:
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Immunity. 2012 Jun 29;36(6):899-901
[PMID:
22749348
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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