title: Regulation of a late phase of T cell polarity and effector functions by Crtam.
abstract: Spatial organization of cellular proteins plays an important role in establishment of cellular polarity to regulate cell division, differentiation, migration, and organogenesis. Activation of T cells by antigen-presenting cells (APCs) results in the formation of an immunological synapse (IS), assembly of a signaling scaffold at the T cell receptor (TCR) contact, cytoskeletal reorganization, and generation of second messengers within the first hours following intercellular contact. We demonstrate here that Crtam (class-I MHC-restricted T-cell associated molecule), an immunoglobulin-superfamily transmembrane protein, coordinates a signaling complex anchored by the Scrib polarity protein to establish a later phase of T cell polarity on a subset of CD4+ T cells >6 hours following activation. Maintenance of this late cellular polarity results in the ability of CD4+Crtam+ T cells to selectively produce more IFNgamma and IL22. Crtam engagement thus modulates signals many hours beyond the initial activation event and dynamically influences the adaptive immune response.
authors.affiliation: Department of Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Jung-Hua
authors.initials: JH
authors.lastname: Yeh
authors.forename: Sachdev S
authors.initials: SS
authors.lastname: Sidhu
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chan
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D016764:Cell Polarity; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism; D007136:Immunoglobulins / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D007136:Immunoglobulins; D007371:Interferon-gamma; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D011948:Receptors, Antigen, T-Cell; D000097043:Interleukin-22; C408522:class-I restricted T cell-associated molecule; C508433:scrib protein, mouse