Modulation of T cell activation by stomatin-like protein 2.

Journal article

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.

Authors: Kirchhof, MG; Chau, L; Lemke, C; Vardhana, S; Darlington, P

• Journal: Journal of Immunology
• Volume: 181
• Issue: 3
• Pages: 1927-1936
• Publication date: 2008-08-01
• DOI: 10.4049/jimmunol.181.3.1927
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: RNA, Small Interfering; Up-Regulation; Actins; Protein Binding; Blood Proteins; Cells, Cultured; Interleukin-2; Lymphocyte Activation; Protein Transport; Membrane Proteins; Receptors, Antigen, T-Cell; Lymphoid Tissue; T-Lymphocytes; Humans; B-Lymphocytes