title: Single cell analysis reveals similar functional competence of dominant and nondominant CD8 T-cell clonotypes.
abstract: Immune protection from infectious diseases and cancer is mediated by individual T cells of different clonal origin. Their functions are tightly regulated but not yet fully characterized. Understanding the contribution of each T cell will improve the prediction of immune protection based on laboratory assessment of T-cell responses. Here we developed techniques for simultaneous molecular and functional assessment of single CD8 T cells directly ex vivo. We studied two groups of patients with melanoma after vaccination with two closely related tumor antigenic peptides. Vaccination induced T cells with strong memory and effector functions, as found in virtually all T cells of the first patient group, and fractions of T cells in the second group. Interestingly, high functionality was not restricted to dominant clonotypes. Rather, dominant and nondominant clonotypes acquired equal functional competence. In parallel, this was also found for EBV- and CMV-specific T cells. Thus, the nondominant clonotypes may contribute similarly to immunity as their dominant counterparts.
authors.affiliation: Ludwig Center for Cancer Research, University of Lausanne, Lausanne CH-1011, Switzerland. daniel.speiser@hospvd.ch
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
authors.forename: Sébastien
authors.initials: S
authors.lastname: Wieckowski
authors.forename: Bhawna
authors.initials: B
authors.lastname: Gupta
authors.forename: Emanuela M
authors.initials: EM
authors.lastname: Iancu
authors.forename: Petra
authors.initials: P
authors.lastname: Baumgaertner
authors.forename: Lukas
authors.initials: L
authors.lastname: Baitsch
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rufer
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D019496:Cancer Vaccines / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002999:Clone Cells; D003587:Cytomegalovirus / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D020869:Gene Expression Profiling; D006801:Humans; D008545:Melanoma / Q000276:immunology; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D059010:Single-Cell Analysis / Q000379:methods*; D013045:Species Specificity; D014611:Vaccination; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D011948:Receptors, Antigen, T-Cell; D022223:Vaccines, Subunit