title: Antigen recognition is facilitated by invadosome-like protrusions formed by memory/effector T cells.
abstract: Adaptive immunity requires that T cells efficiently scan diverse cell surfaces to identify cognate Ag. However, the basic cellular mechanisms remain unclear. In this study, we investigated this process using vascular endothelial cells, APCs that possess a unique and extremely advantageous, planar morphology. High-resolution imaging revealed that CD4 memory/effector T cells dynamically probe the endothelium by extending submicron-scale, actin-rich "invadosome/podosome-like protrusions" (ILPs). The intimate intercellular contacts enforced by ILPs consistently preceded and supported T cell activation in response to endothelial MHC class II/Ag. The resulting calcium flux stabilized dense arrays of ILPs (each enriched in TCR, protein kinase C-θ, ZAP70, phosphotyrosine, and HS1), forming what we term a podo-synapse. Similar findings were made using CD8 CTLs on endothelium. Furthermore, careful re-examination of both traditional APC models and professional APCs suggests broad relevance for ILPs in facilitating Ag recognition. Together, our results indicate that ILPs function as sensory organelles that serve as actuators of immune surveillance.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Sage
authors.forename: Laya M
authors.initials: LM
authors.lastname: Varghese
authors.forename: Roberta
authors.initials: R
authors.lastname: Martinelli
authors.forename: Tracey E
authors.initials: TE
authors.lastname: Sciuto
authors.forename: Masataka
authors.initials: M
authors.lastname: Kamei
authors.forename: Ann M
authors.initials: AM
authors.lastname: Dvorak
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Springer
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Carman
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016466:CHO Cells; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D020013:Calcium Signaling; D002450:Cell Communication / Q000276:immunology; D022081:Cell Surface Extensions / Q000276:immunology* / Q000648:ultrastructure; D006224:Cricetinae; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D005802:Genes, MHC Class II; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000276:immunology; D057705:Transendothelial and Transepithelial Migration; D014162:Transfection
chemical_list: D000942:Antigens, Bacterial; D011948:Receptors, Antigen, T-Cell; D002118:Calcium