Differential roles for Wiskott-Aldrich syndrome protein in immune synapse formation and IL-2 production.
Wiskott-Aldrich syndrome protein (WASP)-deficient T cells exhibit defects in IL-2 production that are widely believed to stem from primary defects in actin remodeling and immune synapse formation. Surprisingly, however, we find that WASP-deficient T cells responding to Ag-specific APCs polymerize actin and organize talin and PKC theta normally, forming an immune synapse that is stable for at least 3 h. At low doses of peptide, WASP-deficient T cells show less efficient talin and PKC theta polarization. Thus, although WASP may facilitate immune synapse formation at low peptide concentrations, WASP is not required for this process. Defects in IL-2 production are observed even under conditions in which immune synapse formation proceeds normally, suggesting that the role of WASP in regulating IL-2 production is independent of its role in immune synapse formation.
Cannon
Judy L
JL
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Burkhardt
Janis K
JK
D000199:Actins / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D002450:Cell Communication; D002478:Cells, Cultured; D045304:Cytochromes c / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007365:Intercellular Junctions / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009036:Moths; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism; D000074121:Protein Kinase C-theta; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016608:Talin / Q000378:metabolism; D014157:Transcription Factors; D051316:Wiskott-Aldrich Syndrome Protein
D000199:Actins; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007376:Interleukin-2; D007527:Isoenzymes; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D016608:Talin; D014157:Transcription Factors; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D045304:Cytochromes c; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta