The SLAM family of immune-cell receptors

Veillette, André; Latour, Sylvain

doi:10.1016/s0952-7915(03)00041-4

Cited by 105 publications

(87 citation statements)

References 49 publications

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“…2B4, CRACC, and NTB-A belong to the recently defined family of signaling lymphocytic activation molecule (SLAM) 4 -related receptors (SRR) (4,5). One characteristic of SRR is the presence of an immunoreceptor tyrosine-based switch motif (ITSM) in their cytoplasmic tail.…”

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confidence: 99%

Molecular Analysis of NTB-A Signaling: A Role for EAT-2 in NTB-A-Mediated Activation of Human NK Cells

Eissmann

Watzl

2006

The Journal of Immunology

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Engagement of NTB-A on human NK cells by homophilic interaction with NTB-A-expressing target cells can trigger NK cell cytotoxicity, cytokine production, and proliferation. To better understand how NTB-A can activate NK cells, we analyzed the molecular mechanisms of NTB-A signaling. We show that NTB-A is tyrosine phosphorylated in unstimulated human NK cells and associates with SLAM-associated protein (SAP) and EAT-2. This phosphorylation of NTB-A is mediated by Src family kinases and is most likely a result of the homophilic interaction of NTB-A among neighboring NK cells. Stimulation of NK cells by NTB-A-positive targets results in increased NTB-A phosphorylation. The cytoplasmic tail of NTB-A contains three tyrosines, two of which are embedded within an immunoreceptor tyrosine-based switch motif. We generated a NTB-A-negative NK cell line, in which we expressed different mutants of NTB-A. Functional studies showed that the second tyrosine is sufficient and essential for NTB-A-mediated cytotoxicity. EAT-2, but not SAP, is recruited to this second tyrosine, indicating that SAP may be dispensable for this NTB-A function. To further investigate this, we silenced SAP expression in NK cell lines. Functional analysis of these cells showed that NTB-A can mediate NK cell cytotoxicity in the absence of SAP, probably via EAT-2. In contrast, NTB-A-mediated IFN-γ production was greatly reduced in the absence of SAP, demonstrating that cytokine production and cytotoxicity are differentially dependent on SAP and possibly EAT-2.

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confidence: 99%

Molecular Analysis of NTB-A Signaling: A Role for EAT-2 in NTB-A-Mediated Activation of Human NK Cells

Eissmann

Watzl

2006

The Journal of Immunology

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“…2B4'ün stimülasyonu, kendisi dışında, fosfolipaz C, LAT (linker for activating of T cells -T hücrelerin aktivasyonu için aracı molekül) ve VAV gibi hücre içi sinyal makanizmalarında rol alan moleküllerin tirozin fosforilasyonuna ve aktive olmalarına neden olur. NK hücrelerinin uyarımı için 2B4 aktivasyonu dışında, CD16 (FcγRIII) ve doğal sitotoksik reseptörlerinde stimülasyonu gereklidir (19). Fizyolojik koşullarda stimülan etkileri olan 2B4 reseptörü XLP hastalarında inhibitör sinyallere yol açarak EBV enfekte B hücrelerinin yok edilmesini engellemektedir (22).…”

Section: ö öZ Ze Et Tunclassified

X'e Bağli Geçi̇ş Gösteren Lenfoproli̇ferati̇f Sendrom: Kli̇ni̇k, Patogenez Ve Geneti̇kle İlgi̇li̇ Geli̇şmeler

Mutlu;İKİNCİOĞULLARI¹

2004

Ankara Üniversitesi Tıp Fakültesi Mecmuası

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“…15,16 The SLAM/CD2 gene cluster, another immunoregulatory family, contains seven adhesion/costimulatory molecules that influence a wide variety of immune system functions. 17,18 We recently identified extensive polymorphisms throughout the SLAM/CD2 gene cluster, which distinguish two stable SLAM/CD2 haplotypes in laboratory mouse strains. Interestingly, while autoimmunity was associated with the more common of these haplotypes, disease only occurred when this version of the SLAM/CD2 cluster was expressed in the context of the C57BL/6 (B6) genome.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations

et al. 2007

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The evolutionary origin of genetic diversity in the SLAM/CD2 gene cluster, implicated in autoimmune lupus susceptibility in mice, was investigated by sequence analysis of exons from six members of the cluster in 48 wild mouse samples derived from the global mouse population. A total of 80 coding region SNPs were identified among the six genes analyzed, indicating that this gene cluster is highly polymorphic in natural mouse populations. Phylogenetic analyses of these allelic sequences revealed clustering of alleles derived from multiple Mus species and subspecies, indicating alleles at several SLAM/CD2 loci were present in ancestral Mus populations prior to speciation and have persisted as polymorphisms for more than 1 million years. Analyses of nonsynonymous/synonymous ratios using likelihood codon substitution models identified several segments in Cd229, Cd48 and Cd84 that were impacted by positive diversifying selective pressures. These findings support the interpretation that selection favoring the generation and retention of functional polymorphisms has played a role in the evolutionary origin of genetic polymorphisms that are predisposing to autoimmunity.

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The SLAM family of immune-cell receptors

Cited by 105 publications

References 49 publications

Molecular Analysis of NTB-A Signaling: A Role for EAT-2 in NTB-A-Mediated Activation of Human NK Cells

Molecular Analysis of NTB-A Signaling: A Role for EAT-2 in NTB-A-Mediated Activation of Human NK Cells

X'e Bağli Geçi̇ş Gösteren Lenfoproli̇ferati̇f Sendrom: Kli̇ni̇k, Patogenez Ve Geneti̇kle İlgi̇li̇ Geli̇şmeler

Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations

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