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T cell activation through the Ag receptor (TCR) requires sustained signaling from signalosomes within lipid raft microdomains in the plasma membrane. In a proteomic analysis of lipid rafts from human T cells, we identified stomatin-like protein (SLP)-2 as a candidate molecule involved in T cell activation through the Ag receptor. In this study, we show that SLP-2 expression in human primary lymphocytes is up-regulated following in vivo and ex vivo activation. In activated T cells, SLP-2 interacts with components of TCR signalosomes and with polymerized actin. More importantly, up-regulation of SLP-2 expression in human T cell lines and primary peripheral blood T cells increases effector responses, whereas down-regulation of SLP-2 expression correlates with loss of sustained TCR signaling and decreased T cell activation. Our data suggest that SLP-2 is an important player in T cell activation by ensuring sustained TCR signaling, which is required for full effector T cell differentiation, and point to SLP-2 as a potential target for immunomodulation.

Original publication

DOI

10.4049/jimmunol.181.3.1927

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

08/2008

Volume

181

Pages

1927 - 1936

Addresses

FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, and Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.

Keywords

Lymphoid Tissue, B-Lymphocytes, T-Lymphocytes, Cells, Cultured, Humans, Actins, Blood Proteins, Membrane Proteins, Receptors, Antigen, T-Cell, RNA, Small Interfering, Interleukin-2, Lymphocyte Activation, Up-Regulation, Protein Binding, Protein Transport