Document Detail

The receptor Ly108 functions as a SAP adaptor-dependent on-off switch for T cell help to B cells and NKT cell development.
MedLine Citation:
PMID:  22683125     Owner:  NLM     Status:  MEDLINE    
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.
Robin Kageyama; Jennifer L Cannons; Fang Zhao; Isharat Yusuf; Christopher Lao; Michela Locci; Pamela L Schwartzberg; Shane Crotty
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2012-06-07
Journal Detail:
Title:  Immunity     Volume:  36     ISSN:  1097-4180     ISO Abbreviation:  Immunity     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-09-13     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9432918     Medline TA:  Immunity     Country:  United States    
Other Details:
Languages:  eng     Pagination:  986-1002     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Division of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, CA 92037, USA.
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MeSH Terms
Amino Acid Motifs
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, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Natural Killer T-Cells / cytology*
Phosphoric Monoester Hydrolases / physiology
Phosphotyrosine / physiology
Protein Processing, Post-Translational
Grant Support
Reg. No./Substance:
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,4,5-trisphosphate 5-phosphatase
Comment In:
Immunity. 2012 Jun 29;36(6):899-901   [PMID:  22749348 ]

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