title: Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor.
abstract: The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ-CD8 interactions require CD8-MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck.
authors.affiliation: 1] Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore [2] Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Casas
authors.affiliation: 1] Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore [2] Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Brzostek
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, USA.
authors.forename: Veronika I
authors.initials: VI
authors.lastname: Zarnitsyna
authors.affiliation: George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, USA.
authors.forename: Jin-sung
authors.initials: JS
authors.lastname: Hong
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore.
authors.forename: Qianru
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: John A H
authors.initials: JA
authors.lastname: Hoerter
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Guo
authors.initials: G
authors.lastname: Fu
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Ampudia
authors.affiliation: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh EH9 3FL, Scotland, UK.
authors.forename: Rose
authors.initials: R
authors.lastname: Zamoyska
authors.affiliation: 1] Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, USA [2] George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: 1] Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore [2] Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Nicholas R J
authors.initials: NR
authors.lastname: Gascoigne
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism*; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism*; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D016827:CD8 Antigens; D018398:Homeodomain Proteins; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; C064658:RAG-1 protein; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)