Modulation of T cell activation by stomatin-like protein 2.
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.
Kirchhof
Mark G
MG
FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, and Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
Chau
Luan A
LA
Lemke
Caitlin D
CD
Vardhana
Santosh
S
Darlington
Peter J
PJ
Márquez
Maria E
ME
Taylor
Roy
R
Rizkalla
Kamilia
K
Blanca
Isaac
I
Dustin
Michael L
ML
Madrenas
Joaquín
J
D000199:Actins / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008221:Lymphoid Tissue / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation
D000199:Actins; D001798:Blood Proteins; D007376:Interleukin-2; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; C406287:STOML2 protein, human