Romero, X. et al. Differential expression of SAP and EAT-2-binding leukocyte cell-surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4). Tissue Antigens 64, 132-144

University of Barcelona, Barcino, Catalonia, Spain
Tissue Antigens (Impact Factor: 2.14). 09/2004; 64(2):132-44. DOI: 10.1111/j.1399-0039.2004.00247.x
Source: PubMed


The CD150 (SLAM) family consists of nine leukocyte cell-surface proteins involved in lymphocyte activation that belong to the immunoglobulin (Ig) superfamily. Six members of this family--CD84, CD150 (SLAM), CD229 (Ly9), CD244 (2B4), NTB-A, and CS1--associate with adapter proteins--SLAM-associated protein (SAP) and EAT-2. SAP is a short intracellular molecule that is mutated in humans with X-linked lymphoproliferative disease. Flow cytometric analysis of the expression of CD84, CD150, CD229, and CD244 cell-surface receptors on several leukocyte and lymphocyte subsets was performed. CD84 and CD150 were present on thymocytes, mature T cells and antigen-presenting cells. The expression of CD84 and CD150 was high on memory T cells. CD150 expression was strongly up-regulated after cell activation. In contrast to CD84, CD150 was absent on resting monocytes and immature dendritic cells (DCs). CD229 presented a pattern of expression restricted to lymphocytes. CD244 was preferentially expressed on natural killer cells, CD8(+) effector cells, resting monocytes, basophils, and eosinophils. We describe a broader distribution of CD84, CD150, CD229, and CD244 than previously reported and show that they are differentially expressed on hematopoietic cells. The heterogeneous expression of these receptors indicates that these molecules may play non-redundant functions in the regulation of both innate and adaptive immune responses.

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    • "CD244 (also called 2B4) is a member of the signaling lymphocyte activation molecule (SLAM) family of immune cell receptors [15], [16], [17]. It is expressed on natural killer (NK) cells, CD4 and CD8 T cells, γδ T cells, monocytes, eosinophils and basophiles [18]. The function of CD244/2B4 on NK cells has been studied extensively; it was initially described as an activating receptor and was later found to have both activating and inhibitory functions in mouse NK cells [15], [16], [19], [20], [21]. "
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    ABSTRACT: CD244 (2B4) is a member of the signaling lymphocyte activation molecule (SLAM) family of immune cell receptors and it plays an important role in modulating NK cell and CD8(+) T cell immunity. In this study, we investigated the expression and function of CD244/2B4 on CD4(+) T cells from active TB patients and latent infection individuals. Active TB patients had significantly elevated CD244/2B4 expression on M. tuberculosis antigen-specific CD4(+) T cells compared with latent infection individuals. The frequencies of CD244/2B4-expressing antigen-specific CD4(+) T cells were significantly higher in retreatment active TB patients than in new active TB patients. Compared with CD244/2B4-dull and -middle CD4(+) T cells, CD244/2B4-bright CD4(+) T cell subset had significantly reduced expression of IFN-γ, suggesting that CD244/2B4 expression may modulate IFN-γ production in M. tuberculosis antigen-responsive CD4(+) T cells. Activation of CD244/2B4 signaling by cross-linking led to significantly decreased production of IFN-γ. Blockage of CD244/2B4 signaling pathway of T cells from patients with active TB resulted in significantly increased production of IFN-γ, compared with isotype antibody control. In conclusion, CD244/2B4 signaling pathway has an inhibitory role on M. tuberculosis antigen-specific CD4(+) T cell function.
    Preview · Article · Apr 2013 · PLoS ONE
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    • "To our knowledge neither SLAM (CD150) nor 2B4, the two main interactors of SAP, are expressed in Jurkat T cells [37]. Using a specific serum (Figure 2B) we show that NTB-A co-migrates with the phosphorylated p70 protein that associates with SAP. "
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    ABSTRACT: Mutations altering the gene encoding the SLAM associated protein (SAP) are responsible for the X-linked lymphoproliferative disease or XLP1. Its absence is correlated with a defective NKT cells development, a decrease in B cell functions and a reduced T cells and NK cells cytotoxic activities, thus leading to an immunodeficiency syndrome. SAP is a small 128 amino-acid long protein that is almost exclusively composed of an SH2 domain. It has been shown to interact with the CD150/SLAM family of receptors, and in a non-canonical manner with SH3 containing proteins such as Fyn, βPIX, PKCθ and Nck1. It would thus play the role of a minimal adaptor protein. It has been shown that SAP plays an important function in the activation of T cells through its interaction with the SLAM family of receptors. Therefore SAP defective T cells display a reduced activation of signaling events downstream of the TCR-CD3 complex triggering. In the present work, we evidence that SAP is a direct interactor of the CD3ζ chain. This direct interaction occurs through the first ITAM of CD3ζ, proximal to the membrane. Additionally, we show that, in the context of the TCR-CD3 signaling, an Sh-RNA mediated silencing of SAP is responsible for a decrease of several canonical T cell signaling pathways including Erk, Akt and PLCγ1 and to a reduced induction of IL-2 and IL-4 mRNA. Altogether, we show that SAP plays a central function in the T cell activation processes through a direct association with the CD3 complex.
    Preview · Article · Aug 2012 · PLoS ONE
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    • "As example we can consider the first cluster of up-regulated genes in monoblasts: this cluster, on chromosome 1q23 (spanning 2 Mb), contains 5 genes significantly up-regulated in monoblasts as compared with CD34+: among them HSPA6 (HSP70B) [49], regulating monocytes maturation towards dendritic cells; FCER1G [50], IgE receptor subunit expressed also in monocytes; SLAMF8 (BLAME) [51] and SLAMF1 [52], that are involved in lymphocytes activation. This genomic region contains a total of 73 EntrezGenes including 11 hypothetical proteins; eight IgG receptors (FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCGR3B, FCRLM1, FCRLM2, FCRL6); and other antigens, belonging to SLAM family, that are involved in regulation of leucocytes activity (CD48 [53]; CD84 [54]; CD244, SLAMF9, SLAMF6, SLAMF7, Ly9 [55]). More genes related to mono/macrophagic functions can be found also within the other clusters of up-regulated genes, such as the genes of MHC class II, involved in antigen presentation. "
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    ABSTRACT: Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where multipotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. Gene expression data from 24 experiments for 8 different cell types of the human myelopoietic lineage were used to generate an integrated myelopoiesis dataset of 9,425 genes, each reliably associated to a unique genomic position and chromosomal coordinate. Lists of genes constitutively expressed or silent during myelopoiesis and of genes differentially expressed in commitment phase of myelopoiesis were first identified using a classical data analysis procedure. Then, the genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. This approach allowed identifying specific chromosomal regions significantly highly or weakly expressed, and clusters of differentially expressed genes and of transcripts related to specific functional modules. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
    Full-text · Article · Feb 2007 · BMC Genomics
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