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SH2D1A and SLAM protein expression in human lymphocytes and derived cell lines
N Nagy1, C Cerboni, K Mattsson
1Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden. Noemi.Nagy@mtc.ki.se
Abstract:
The gene defect responsible for the X-linked lymphoproliferative disease (XLP) is associated with an impaired control of Epstein-Barr virus (EBV) infection. The gene has been recently identified and the encoded protein (designated SH2D1A, DSHP or SAP) was characterized. It is a 128 amino acid (aa) protein, containing a single Src homology 2 (SH2) domain. It interacts with signaling lymphocytic activation molecule (SLAM) expressed on the surface of activated T and B cells. We show that activated T, but not activated B, cells express the SH2D1A protein. NK cells express the protein as well. Tumor lines originating from B, T or NK cells exhibited similar SH2D1A protein expression as the corresponding normal cells, with some notable exceptions. EBV-carrying, tumor phenotype representative (type I), but not EBV-carrying lymphoblastoid cell line (LCL)-like (type III) or EBV-negative Burkitt lymphoma (BL) lines expressed SH2D1A. The phenotypic switch from type I to type III in the EBV-carrying BL line Mutu was associated with a down-regulation of SH2D1A and up-regulation of SLAM. In contrast to normal ex vivo and long-term activated NK cells, 2 of 3 NK leukemia lines expressed SLAM. All 3 lines expressed SH2D1A, like their normal counterparts.
Insights
X-linked lymphoproliferative disease (XLP) involves impaired Epstein-Barr virus (EBV) control. The SH2D1A protein interacts with SLAM on immune cells, but its expression varies in EBV-associated tumors.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- X-linked lymphoproliferative disease (XLP) is linked to defective Epstein-Barr virus (EBV) control.
- The SH2D1A protein, encoded by the XLP-associated gene, contains a Src homology 2 (SH2) domain.
- SH2D1A interacts with Signaling Lymphocytic Activation Molecule (SLAM) on activated immune cells.
Purpose of the Study:
- To characterize the expression of the SH2D1A protein in various immune cells and tumor lines.
- To investigate the relationship between SH2D1A expression, SLAM, and EBV infection status in B cell lymphomas.
- To examine SH2D1A and SLAM expression in NK cells and NK leukemia lines.
Main Methods:
- Immunoblotting or Western blotting to detect SH2D1A protein expression.
- Analysis of SH2D1A and SLAM expression in normal activated T cells, B cells, and NK cells.
- Characterization of SH2D1A and SLAM expression in various tumor cell lines, including EBV-positive and EBV-negative Burkitt lymphoma lines and NK leukemia lines.
Main Results:
- SH2D1A protein is expressed in activated T cells and NK cells, but not in activated B cells.
- EBV-carrying type I Burkitt lymphoma (BL) lines expressed SH2D1A, whereas EBV-carrying type III BL lines and EBV-negative BL lines did not.
- A phenotypic switch from type I to type III in EBV-carrying BL lines correlated with SH2D1A down-regulation and SLAM up-regulation.
- NK leukemia lines expressed SH2D1A, with variable SLAM expression.
Conclusions:
- SH2D1A expression is cell-type specific and influenced by EBV infection status and cellular phenotype.
- The interplay between SH2D1A and SLAM may be critical in the pathogenesis of EBV-associated B cell malignancies.
- SH2D1A is expressed in NK leukemia, suggesting a potential role in NK cell malignancies.