title: Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8+ T cells.
abstract: Tissue-resident memory CD8+T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRMcell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRMcell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector. We found that CD8+T cells of different specificities underwent antigen-dependent competition in the infected tissue, which shaped the composition of the local pool of TRMcells. This local cross-competition was active for T cells recognizing antigens that are coexpressed by infected cells. In contrast, TRMcell development remained largely undisturbed by the presence of potential competitors when antigens expressed in the same tissue were segregated through infection with antigenically distinct viral quasispecies. Functionally, local cross-competition might serve as a gatekeeping mechanism to regulate access to the resident memory niche and to fine-tune the local repertoire of antiviral TRMcells.
authors.affiliation: Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany.|Klinikum rechts der Isar, Department of Neurology, Technische Universität München, 81675 Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Muschaweckh
authors.affiliation: Institute for Medical Microbiology, Immunology, and Hygiene, Technische Universität München, 81675 Munich, Germany.
authors.forename: Veit R
authors.initials: VR
authors.lastname: Buchholz
authors.affiliation: Institute of Medical Microbiology and Hygiene and Forschungszentrum für Immuntherapie, University of Mainz Medical Center, 55131 Mainz, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Fellenzer
authors.affiliation: Institute of Medical Microbiology and Hygiene and Forschungszentrum für Immuntherapie, University of Mainz Medical Center, 55131 Mainz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hessel
authors.affiliation: Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany.|Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
authors.forename: Paul-Albert
authors.initials: PA
authors.lastname: König
authors.affiliation: Institute for Virology, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität, 40225 Düsseldorf, Germany.
authors.forename: Sha
authors.initials: S
authors.lastname: Tao
authors.affiliation: Institute for Virology, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität, 40225 Düsseldorf, Germany.
authors.forename: Ronny
authors.initials: R
authors.lastname: Tao
authors.affiliation: Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwälder
authors.affiliation: Institute for Medical Microbiology, Immunology, and Hygiene, Technische Universität München, 81675 Munich, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Klinikum rechts der Isar, Department of Neurology, Technische Universität München, 81675 Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Korn
authors.affiliation: Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany.|Institute of Experimental Immunology, Universität Bonn, 53105 Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kastenmüller
authors.affiliation: Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany Ingo.Drexler@med.uni-duesseldorf.de georg.gasteiger@uniklinik-freiburg.de.|Institute for Virology, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität, 40225 Düsseldorf, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Drexler
authors.affiliation: Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany Ingo.Drexler@med.uni-duesseldorf.de georg.gasteiger@uniklinik-freiburg.de.|Institute of Medical Microbiology and Hygiene and Forschungszentrum für Immuntherapie, University of Mainz Medical Center, 55131 Mainz, Germany.|Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Center, 79104 Freiburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Gasteiger
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014615:Vaccinia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D011948:Receptors, Antigen, T-Cell