A novel receptor involved in T-cell activation

Cocks, Benjamin G.; Chang, Cheng-Shyong; Carballido, J; Yssel, Hans; Vries, J E de; Aversa, Gregorio

doi:10.1038/376260a0

Cited by 428 publications

(397 citation statements)

References 23 publications

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“…SLAM is a host cell receptor for both vaccine and WT MV strains of MV. It is a 70-kDa, type I transmembrane glycoprotein expressed on immune cells such as activated T cells, B cells, macrophages, and dendritic cells (DC) (10). The N-terminal V domain of SLAM interacts with the hemagglutinin protein of MV (9).…”

Section: Easles Viruses (Mv) Is One Of the Most Contagious Diseasesmentioning

confidence: 99%

Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice

Welstead

Iorio

Draker

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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A transgenic mouse containing the complete human SLAM (hSLAM͞CD150) gene, including its endogenous promoter for transcription, was generated by using human genomic DNA cloned into a bacterial artificial chromosome. hSLAM, the primary receptor for measles viruses (MV), was expressed on activated B, T, and dendritic cells with an expression profile equivalent to that of humans. We demonstrated that hSLAM ؉ cells obtained from the transgenic mouse, including activated B, T, and dendritic cells, were susceptible to MV infection in a receptor-dependent manner. Evidence was provided for transient infection in the nasal lymph nodes of hSLAM ؉ mice after intranasal inoculation. Virus was rapidly cleared without signs of secondary replication. To improve the efficiency of MV production, the hSLAM ؉ mice were bred with mice having a Stat1-deficient background. These mice were more susceptible to MV infection and produced more virus particles. After intranasal and intraperitoneal inoculation of these mice with MV, infections of the thymus, spleen, nasal, mesenteric, and leg lymph nodes were detected. Upon necropsy, enlarged lymph nodes and spleen were apparent. Flow cytometric analysis showed that abnormally large numbers of mature neutrophils and natural killer cells caused the splenomegaly. The hSLAM transgenic mouse constitutes an improved rodent model for studying the interaction of MV with immune cells that more accurately reflects the infection pattern found in humans.activated lymphocytes ͉ transgenic mouse ͉ dendritic cells M easles viruses (MV) is one of the most contagious diseases known to man and is a major killer of children in the developing countries of Africa and South America. The high mortality rate associated with MV infection results from increased susceptibility to opportunistic infections. Although MV has been studied extensively, the mechanism for the immunosuppressive effects observed during MV infection remains unclear (1).The development of a mouse model may lead to a better understanding of the immune suppression induced by MV. This was previously attempted by expressing CD46, one of the two receptors for MV, in mice (2-6). However, CD46 receptor, a ubiquitously expressed glycoprotein, is only used by vaccine or laboratory adapted strains of MV. Recently, a second receptor for MV was discovered: CD150 or signaling lymphocytic activation molecule (SLAM) (7-9). SLAM is a host cell receptor for both vaccine and WT MV strains of MV. It is a 70-kDa, type

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Section: Easles Viruses (Mv) Is One Of the Most Contagious Diseasesmentioning

confidence: 99%

Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice

Welstead

Iorio

Draker

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…It is expressed by CD45RO+ T-cells, immature by guest on http://www.jbc.org/ Downloaded from thymocytes, and a proportion of B-cells, and is rapidly upregulated upon the activation of T cells, B cells and dendritic cells (11,15,16) but not NK cells (17). It has been shown in mice that highly polarized Th1 but not Th2 cells express high levels of SLAM (17).…”

Section: Introductionmentioning

confidence: 99%

“…SLAM was initially identified with a monoclonal antibody (mAb) that activated T cells and bound a previously uncharacterised activation antigen (11). It is expressed by CD45RO+ T-cells, immature by guest on http://www.jbc.org/ Downloaded from thymocytes, and a proportion of B-cells, and is rapidly upregulated upon the activation of T cells, B cells and dendritic cells (11,15,16) but not NK cells (17).…”

Section: Introductionmentioning

confidence: 99%

Signaling Lymphocytic Activation Molecule (CDw150) Is Homophilic but Self-associates with Very Low Affinity

Mavaddat¹,

Mason²,

Atkinson³

et al. 2000

Journal of Biological Chemistry

126

104

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“…6) was identified as SLAM (signaling lymphocytic activation molecule-associated protein)-associated protein (SAP; also known as DSHP and SH2D1A) and encodes a small SH2-domain containing protein (7)(8)(9). SAP interacts with a unique tyrosine-based motif (TxYxxV/I) present in the cytoplasmic domains of 2B4 and SLAM (7, 10 -12), cell surface molecules that, when ligated, result in activation of NK cells and T cells, respectively (13)(14)(15). The association between SAP and 2B4 or SLAM prevented the recruitment of the protein tyrosine phosphatase SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) to the cytoplasmic domain of tyrosyl-phosphorylated 2B4 and SLAM (7,10,12).…”

mentioning

confidence: 99%

Cutting Edge: Functional Requirement for SAP in 2B4-Mediated Activation of Human Natural Killer Cells as Revealed by the X-Linked Lymphoproliferative Syndrome

Tangye

Phillips

Lanier

et al. 2000

The Journal of Immunology

241

185

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X-linked lymphoproliferative syndrome (XLP) is an immunodeficiency characterized by life-threatening infectious mononucleosis and EBV-induced B cell lymphoma. The gene mutated in XLP encodes SLAM (signaling lymphocytic activation molecule-associated protein)-associated protein (SAP), a small SH2 domain-containing protein. SAP associates with 2B4 and SLAM, activating receptors expressed by NK and T cells, and prevents recruitment of SH2 domain-containing protein tyrosine phosphatase-2 SHP-2) to the cytoplasmic domains of these receptors. The phenotype of XLP may therefore result from perturbed signaling through SAP-associating receptors. We have addressed the functional consequence of SAP deficiency on 2B4-mediated NK cell activation. Ligating 2B4 on normal human NK cells with anti-2B4 mAb or interaction with transfectants bearing the 2B4 ligand CD48 induced NK cell cytotoxicity. In contrast, ligation of 2B4 on NK cells from a SAP-deficient XLP patient failed to initiate cytotoxicity. Despite this, CD2 or CD16-induced cytotoxicity of SAP-deficient NK cells was similar to that of normal NK cells. Thus, selective impairment of 2B4-mediated NK cell activation may contribute to the immunopathology of XLP.

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A novel receptor involved in T-cell activation

Cited by 428 publications

References 23 publications

Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice

Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice

Signaling Lymphocytic Activation Molecule (CDw150) Is Homophilic but Self-associates with Very Low Affinity

Cutting Edge: Functional Requirement for SAP in 2B4-Mediated Activation of Human Natural Killer Cells as Revealed by the X-Linked Lymphoproliferative Syndrome

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