Article

Differential expression of SAP and EAT-2-binding leukocyte cell-surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4)

University of Barcelona, Barcino, Catalonia, Spain
Tissue Antigens (Impact Factor: 2.35). 09/2004; 64(2):132-44. DOI: 10.1111/j.1399-0039.2004.00247.x
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
159 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Haematologica 2011 [Epub ahead of print] Citation:. Surface molecule CD229 as a novel target for the diagnosis and treatment of multiple myeloma. Haematologica. 2011; 96:xxx doi:10.3324/haematol.2010.036814 Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process. Haematologica (pISSN: 0390-6078, eISSN: 1592-8721, NLM ID: 0417435, www.haemato-logica.org) publishes peer-reviewed papers across all areas of experimental and clinical hematology. The journal is owned by the Ferrata Storti Foundation, a non-profit organiza-tion, and serves the scientific community with strict adherence to the principles of open access publishing (www.doaj.org). In addition, the journal makes every paper published immediately available in PubMed Central (PMC), the US National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: X-linked lymphoproliferative disease (XLP) is an inherited immune defect caused by mutations in the Src homology 2 domain-containing gene 1A, which encodes the adapter protein, signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). SAP is expressed in T cells, natural killer (NK) cells, and NKT cells, where it binds to the cytoplasmic domain of the surface receptor SLAM (CD150) and the related receptors, 2B4 (CD244), CD84, Ly9 (CD229), NK-T-B-antigen, and CD2-like receptor-activating cytotoxic T cells. SAP also binds to the Src family tyrosine kinase Fyn and recruits it to SLAM, which leads to the generation of downstream phosphotyrosine signals. While the roles of the SLAM family receptors are only beginning to be understood, experiments suggest that these molecules regulate important aspects of lymphocyte function, such as proliferation, cytokine secretion, cytotoxicity, and antibody production. Thus, in XLP patients who lack functional SAP, the SLAM family receptors may not signal properly. This property likely contributes to the phenotypes of XLP, including fulminant infectious mononucleosis, lymphoma, and hypogammaglobulinemia. Further studies of SAP and the SLAM family receptors will provide insights into XLP and elucidate the signaling events regulating lymphocyte ontogeny and function.
    Immunological Reviews 03/2005; 203(1):180-99. DOI:10.1111/j.0105-2896.2005.00230.x · 12.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CD229 is a member of the CD150 family of the Ig superfamily expressed on T and B cells. Receptors of this family regulate cytokine production and cytotoxicity of lymphocytes and NK cells. The cytoplasmic tail of CD229 binds to SAP, a protein that is defective in X-linked lymphoproliferative syndrome. To identify the CD229 ligand, we generated a soluble Ig fusion protein containing the two N-terminal extracellular domains of human CD229 (CD229-Ig). CD229-Ig bound to CD229-transfected cells, whereas no binding was detected on cells expressing other CD150 family receptors, showing that CD229 binds homophilically. Both human and mouse CD229 interacted with itself. Domain deletion mutants showed that the N-terminal Ig-domain mediates homophilic adhesion. CD229-CD229 binding was severely compromised when the charged amino acids E27 and E29 on the predicted B-C loop and R89 on the F-G loop of the N-terminal domain were mutated to alanine. In contrast, one mutation, R44A, enhanced the homophilic interaction. Confocal microscopy image analysis revealed relocalization of CD229 to the contact area of T and B cells during Ag-dependent immune synapse formation. Thus, CD229 is its own ligand and participates in the immunological synapse.
    The Journal of Immunology 07/2005; 174(11):7033-42. DOI:10.4049/jimmunol.174.11.7033 · 5.36 Impact Factor