Optimal T cell activation and expansion require engagement of the TCR plus costimulatory signals delivered through accessory molecules. SLAM (signaling lymphocytic activation molecule), a 70-kDa costimulatory molecule belonging to the Ig superfamily, was defined as a human cell surface molecule that mediated CD28-independent proliferation of human T cells and IFN-γ production by human Th1 and Th2 clones. In this study, we describe the cloning of mouse SLAM and the production of mAb against it which reveal its expression on primary mouse T and B cells. Mouse SLAM is expressed on highly polarized Th1 and Th2 populations, and is maintained on Th1, but not on Th2 clones. Anti-mouse SLAM mAb augmented IFN-γ production by Th1 cells and Th1 clones stimulated through the TCR, but did not induce IFN-γ production by Th2 cells, nor their production of IL-4 or their proliferation. Mouse SLAM is a 75-kDa glycoprotein that upon tyrosine phosphorylation associates with the src homology 2-domain-containing protein tyrosine phosphatase SHP-2, but not SHP-1. Mouse SLAM also associates with the recently described human SLAM-associated protein. These studies may provide new insights into the regulation of Th1 responses.

1

DNAX is supported by the Schering Plough Research Institute. T.M.H. was initially funded by fellowships from the Swiss National Science Foundation and from the Roche Research Foundation, Switzerland.

     

Abbreviations used in this paper: SLAM, signaling lymphocytic activation molecule; AP, alkaline phosphatase; h, human; m, mouse; SAP, SLAM-associated protein; SH2, Src homology 2; SHP, SH2 domain-bearing protein tyrosine phosphatase; XLP, X-linked lymphoproliferative disease; PIG, phosphatidylinositol glycan.

We thank Franck Barrat and Victoria Heath for reviewing the manuscript; Jun Wu and Richard Murray for discussion; Linda Lucian and Chad Crain for technical assistance; Debbie Ligget for oligonucleotide synthesis; Dan Gorman and the DNAX sequencing facility for DNA sequencing; and Jim Cupp, Eleni Callas, Jennifer Maskrey, and Dixie Pollakoff for cell sorting. We thank Maribel Andonian for help with graphics.

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