SH2D1A and SLAM protein expression in human lymphocytes and derived cell lines

The gene defect responsible for the X-linked lymphoproliferative disease (X LP) is associated with an impaired control of Epstein-Barr virus (EBV) infe ction. The gene has been recently identified and the encoded protein (desig nated SH2D1A, DSHP or SAP) was characterized. It is a 128 amino acid (aa) p rotein, containing a single Src homology 2 (SH2) domain. It interacts with signaling lymphocytic activation molecule (SLAM) expressed on the surface o f activated T and B cells. We show that activated T, but not activated B, c ells express the SH2D1A protein. NK cells express the protein as well. Tumo r 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-carryin g lymphoblastoid cell line (LCL)-like (type III) or EBV-negative Burkitt ly mphoma (BL) lines expressed SH2D1A. The phenotypic switch from type I to ty pe III in the EBV-carrying BL line Mutu was associated with a down-regulati on of SH2D1A and up-regulation of SLAM. In contrast to normal ex vivo and l ong-term activated NK cells. 2 of 3 NK leukemia lines expressed SLAM. All 3 lines expressed SH2D1A, like their normal counterparts. Int. J. Cancer 88: 439-447,2000. (C) 2000 Wiley-Liss, Inc.