Regulation of a late phase of T cell polarity and effector functions by Crtam.
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.
Yeh
Jung-Hua
JH
Department of Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Sidhu
Sachdev S
SS
Chan
Andrew C
AC
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
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