The Experts below are selected from a list of 1626 Experts worldwide ranked by ideXlab platform
Pablo Engel - One of the best experts on this subject based on the ideXlab platform.
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Expression of SLAM (CD150) cell-surface receptors on human B-cell subsets: From pro-B to plasma cells
Immunology Letters, 2010Co-Authors: Jose De Salort, Jordi Sintes, Laia Llinàs, Jessica Matesanz-isabel, Pablo EngelAbstract:The SLAM (CD150) family receptors are leukocyte cell-surface glycoproteins involved in leukocyte activation. These molecules and their adaptor protein SAP contribute to the effective germinal center formation, generation of high-affinity antibody-secreting plasma cells, and memory B cells, thereby facilitating long-term humoral immune response. Multi-color flow cytometric analysis was performed to determine the expression of CD48 (SLAMF2), CD84 (SLAMF5), CD150 (SLAM or SLAMF1), CD229 (Ly9 or SLAMF3), CD244 (2B4 or SLAMF4), CD319 (CRACC, CS1, or SLAMF7), and CD352 (NTB-A or SLAMF6) on human cell lines and B-cell subsets. The following subsets were assessed: pro-B, pre-B, immature-B, and mature-B cells from bone marrow; transitional and B1/B2 subsets from peripheral blood; and naive, pre-germinal center, germinal center, memory, plasmablasts, and plasma cells from tonsil and spleen. All receptors were expressed on B cells, with the exception of CD244. SLAM family molecules were widely distributed during B-cell development, maturation and terminal differentiation into plasmablasts and plasma cells, but their expression among various B-cell subsets differed significantly. Such heterogeneous expression patterns suggest that SLAM molecules play an essential and non-redundant role in the control of humoral immune responses.
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the adaptor 3bp2 activates CD244 mediated cytotoxicity in pkc and sap dependent mechanisms
Molecular Immunology, 2008Co-Authors: Ifigenia Saboritvillarroya, Pablo Engel, Agueda Martinezbarriocanal, Irene Olivervila, Joan Sayos, Margarita MartinAbstract:Natural killer (NK) cell cytotoxicity requires triggering of activation receptors over inhibitory receptors. CD244, a member of CD150 receptor family, positively regulates NK-mediated lyses by activating an intracellular multiproteic signaling network that involves the adaptors X-linked lymphoproliferative gene product SAP and 3BP2. However, the exact mechanisms used by 3BP2 to enhance CD244-mediated cytotoxicity are still not fully understood. Here using the human NK cell line YT-overexpressing 3BP2, we found that the adaptor increases CD244, PI3K, and Vav phosphorylation upon CD244 engagement. The use of enzymatic inhibitors revealed that 3BP2-dependent cytolysis enhancement was PKC-dependent and PI3K-ERK independent. Furthermore, 3BP2 overexpression enhanced PKC delta phosphorylation. SAP knockdown expression inhibited PKC delta activation, indicating that the activating role played by 3BP2 depends upon the presence of SAP. In conclusion, our data show that 3BP2 acts downstream of SAP, increases CD244 phosphorylation and links the receptor with PI3K, Vav, PLC gamma, and PKC downstream events in order to achieve maximum NK killing function.
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the adaptor protein 3bp2 binds human CD244 and links this receptor to vav signaling erk activation and nk cell killing
Journal of Immunology, 2005Co-Authors: Ifigenia Saboritvillarroya, Juana M Del Valle, Xavier Romero, Enric Esplugues, Pilar Lauzurica, Pablo Engel, Margarita MartinAbstract:Adaptor proteins, molecules that mediate intermolecular interactions, are crucial for cellular activation. The adaptor 3BP2 has been shown to positively regulate NK cell-mediated cytotoxicity. In this study we present evidence for a physical interaction between 3BP2 and the CD244 receptor. CD244, a member of the CD150 family, is a cell surface protein expressed on NK, CD8+ T, and myeloid cells. CD244 interacts via its Src homology 2 domain with the X-linked lymphoproliferative disease gene product signaling lymphocytic activation molecule-associated protein (SAP)/SH2 domain protein 1A. 3BP2 interacts with human but not murine CD244. CD244-3BP2 interaction was direct and regulated by phosphorylation, as shown by a three-hybrid analysis in yeast and NK cells. Tyr337 on CD244, part of a consensus motif for SAP/SH2 domain protein 1A binding, was critical for the 3BP2 interaction. Although mutation of Tyr337 to phenylalanine abrogated human 3BP2 binding, we still observed SAP association, indicating that this motif is not essential for SAP recruitment. CD244 ligation induced 3BP2 phosphorylation and Vav-1 recruitment. Overexpression of 3BP2 led to an increase in the magnitude and duration of ERK activation, after CD244 triggering. This enhancement was concomitant with an increase in cytotoxicity due to CD244 ligation. However, no differences in IFN-γ secretion were found when normal and 3BP2-transfected cells were compared. These results indicate that CD244-3BP2 association regulates cytolytic function but not IFN-γ release, reinforcing the hypothesis that, in humans, CD244-mediated cytotoxicity and IFN-γ release involve distinct NK pathways.
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differential expression of sap and eat 2 binding leukocyte cell surface molecules cd84 cd150 slam cd229 ly9 and CD244 2b4
Tissue Antigens, 2004Co-Authors: Xavier Romero, D Benitez, Sandra March, R Vilella, M Miralpeix, Pablo EngelAbstract: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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Differential expression of SAP and EAT‐2‐binding leukocyte cell‐surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4)
Tissue Antigens, 2004Co-Authors: Xavier Romero, D Benitez, Sandra March, R Vilella, M Miralpeix, Pablo EngelAbstract: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.
Xavier Romero - One of the best experts on this subject based on the ideXlab platform.
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the adaptor protein 3bp2 binds human CD244 and links this receptor to vav signaling erk activation and nk cell killing
Journal of Immunology, 2005Co-Authors: Ifigenia Saboritvillarroya, Juana M Del Valle, Xavier Romero, Enric Esplugues, Pilar Lauzurica, Pablo Engel, Margarita MartinAbstract:Adaptor proteins, molecules that mediate intermolecular interactions, are crucial for cellular activation. The adaptor 3BP2 has been shown to positively regulate NK cell-mediated cytotoxicity. In this study we present evidence for a physical interaction between 3BP2 and the CD244 receptor. CD244, a member of the CD150 family, is a cell surface protein expressed on NK, CD8+ T, and myeloid cells. CD244 interacts via its Src homology 2 domain with the X-linked lymphoproliferative disease gene product signaling lymphocytic activation molecule-associated protein (SAP)/SH2 domain protein 1A. 3BP2 interacts with human but not murine CD244. CD244-3BP2 interaction was direct and regulated by phosphorylation, as shown by a three-hybrid analysis in yeast and NK cells. Tyr337 on CD244, part of a consensus motif for SAP/SH2 domain protein 1A binding, was critical for the 3BP2 interaction. Although mutation of Tyr337 to phenylalanine abrogated human 3BP2 binding, we still observed SAP association, indicating that this motif is not essential for SAP recruitment. CD244 ligation induced 3BP2 phosphorylation and Vav-1 recruitment. Overexpression of 3BP2 led to an increase in the magnitude and duration of ERK activation, after CD244 triggering. This enhancement was concomitant with an increase in cytotoxicity due to CD244 ligation. However, no differences in IFN-γ secretion were found when normal and 3BP2-transfected cells were compared. These results indicate that CD244-3BP2 association regulates cytolytic function but not IFN-γ release, reinforcing the hypothesis that, in humans, CD244-mediated cytotoxicity and IFN-γ release involve distinct NK pathways.
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differential expression of sap and eat 2 binding leukocyte cell surface molecules cd84 cd150 slam cd229 ly9 and CD244 2b4
Tissue Antigens, 2004Co-Authors: Xavier Romero, D Benitez, Sandra March, R Vilella, M Miralpeix, Pablo EngelAbstract: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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Differential expression of SAP and EAT‐2‐binding leukocyte cell‐surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4)
Tissue Antigens, 2004Co-Authors: Xavier Romero, D Benitez, Sandra March, R Vilella, M Miralpeix, Pablo EngelAbstract: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.
Edith M Janssen - One of the best experts on this subject based on the ideXlab platform.
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CD244 represents a new therapeutic target in head and neck squamous cell carcinoma.
Journal for immunotherapy of cancer, 2020Co-Authors: Laura Agresta, Maria A Lehn, Kristin Lampe, Rachel Cantrell, Cassandra M Hennies, Sara Szabo, Laura Conforti, Kasper Hoebe, Trisha Wise-draper, Edith M JanssenAbstract:Developing novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess the therapeutic potential of CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on a variety of immune cells, including exhausted CD8+ T cells, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs). Using de-identified human tumor and blood samples from patients with head and neck squamous cell carcinoma (HNSCC) and HNSCC models in WT and CD244-/- mice, we assessed the therapeutic potential of CD244 using flow cytometry, RT-PCR, Luminex immunoassays and histopathological analyses. Compared with healthy tissues, tumor infiltrating CD8+ T cells from HNSCC patients and a HNSCC mouse model showed significant increased expression of CD244 expression that correlated with PD1 expression. Moreover, CD244 was increased on intratumoral DC and MDSC and high CD244 expression correlated with PD-L1 expression and increased spontaneous expression of immune-suppressive mediators. In addition, CD244 activation inhibited production of proinflammatory cytokines in human DC in vitro. Importantly, CD244-/- mice showed significantly impaired tumor growth of HNSCC and interventional treatment of WT mice with anti-CD244 monoclonal antibody significantly impaired the growth of established HNSCC tumors and increased tumor-infiltrating CD8+ T cells. Together these data suggest that CD244 contributes to the overall immune-suppressive environment and therefore has potential as a new immunotherapy target in the treatment of malignancies. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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CD244 represents a new therapeutic target in head and neck squamous cell carcinoma
Journal for ImmunoTherapy of Cancer, 2020Co-Authors: Laura Agresta, Maria A Lehn, Kristin Lampe, Rachel Cantrell, Cassandra M Hennies, Sara Szabo, Trisha Wisedraper, Laura Conforti, Kasper Hoebe, Edith M JanssenAbstract:BACKGROUND: Developing novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess the therapeutic potential of CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on a variety of immune cells, including exhausted CD8(+) T cells, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs). METHODS: Using de-identified human tumor and blood samples from patients with head and neck squamous cell carcinoma (HNSCC) and HNSCC models in WT and CD244(-/-) mice, we assessed the therapeutic potential of CD244 using flow cytometry, RT-PCR, Luminex immunoassays and histopathological analyses. RESULTS: Compared with healthy tissues, tumor infiltrating CD8(+) T cells from HNSCC patients and a HNSCC mouse model showed significant increased expression of CD244 expression that correlated with PD1 expression. Moreover, CD244 was increased on intratumoral DC and MDSC and high CD244 expression correlated with PD-L1 expression and increased spontaneous expression of immune-suppressive mediators. In addition, CD244 activation inhibited production of proinflammatory cytokines in human DC in vitro. Importantly, CD244(-/-) mice showed significantly impaired tumor growth of HNSCC and interventional treatment of WT mice with anti-CD244 monoclonal antibody significantly impaired the growth of established HNSCC tumors and increased tumor-infiltrating CD8(+) T cells. CONCLUSIONS: Together these data suggest that CD244 contributes to the overall immune-suppressive environment and therefore has potential as a new immunotherapy target in the treatment of malignancies.
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the emerging role of CD244 signaling in immune cells of the tumor microenvironment
Frontiers in Immunology, 2018Co-Authors: Laura Agresta, Kasper Hoebe, Edith M JanssenAbstract:In cancer, immune exhaustion contributes to the immunosuppressive tumor microenvironment. Exhausted immune cells demonstrate poor effector function and sustained expression of certain immunomodulatory receptors, which can be therapeutically targeted. CD244 is a Signaling Lymphocyte Activation Molecule (SLAM) family immunoregulatory receptor found on many immune cell types – including NK cells, a subset of T cells, DCs, and MDSCs – that represents a potential therapeutic target. Here, we discuss the role of CD244 in tumor-mediated immune cell regulation.
R Vilella - One of the best experts on this subject based on the ideXlab platform.
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differential expression of sap and eat 2 binding leukocyte cell surface molecules cd84 cd150 slam cd229 ly9 and CD244 2b4
Tissue Antigens, 2004Co-Authors: Xavier Romero, D Benitez, Sandra March, R Vilella, M Miralpeix, Pablo EngelAbstract: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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Differential expression of SAP and EAT‐2‐binding leukocyte cell‐surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4)
Tissue Antigens, 2004Co-Authors: Xavier Romero, D Benitez, Sandra March, R Vilella, M Miralpeix, Pablo EngelAbstract: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.
Sandra March - One of the best experts on this subject based on the ideXlab platform.
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differential expression of sap and eat 2 binding leukocyte cell surface molecules cd84 cd150 slam cd229 ly9 and CD244 2b4
Tissue Antigens, 2004Co-Authors: Xavier Romero, D Benitez, Sandra March, R Vilella, M Miralpeix, Pablo EngelAbstract: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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Differential expression of SAP and EAT‐2‐binding leukocyte cell‐surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4)
Tissue Antigens, 2004Co-Authors: Xavier Romero, D Benitez, Sandra March, R Vilella, M Miralpeix, Pablo EngelAbstract: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.