title: Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide.
abstract: The aim of T cell vaccines is the expansion of antigen-specific T cells able to confer immune protection against pathogens or tumors. Although increase in absolute cell numbers, effector functions and TCR repertoire of vaccine-induced T cells are often evaluated, their reactivity for the cognate antigen versus their cross-reactive potential is rarely considered. In fact, little information is available regarding the influence of vaccines on T cell fine specificity of antigen recognition despite the impact that this feature may have in protective immunity. To shed light on the cross-reactive potential of vaccine-induced cells, we analyzed the reactivity of CD8(+) T cells following vaccination of HLA-A2(+) melanoma patients with Melan-A peptide, incomplete Freund's adjuvant and CpG-oligodeoxynucleotide adjuvant, which was shown to induce strong expansion of Melan-A-reactive CD8(+) T cells in vivo. A collection of predicted Melan-A cross-reactive peptides, identified from a combinatorial peptide library, was used to probe functional antigen recognition of PBMC ex vivo and Melan-A-reactive CD8(+) T cell clones. While Melan-A-reactive CD8(+) T cells prior to vaccination are usually constituted of widely cross-reactive naive cells, we show that peptide vaccination resulted in expansion of memory T cells displaying a reactivity predominantly restricted to the antigen of interest. Importantly, these cells are tumor-reactive.
authors.affiliation: Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. victor.appay@chups.jussieu.fr
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rufer
authors.forename: Severine
authors.initials: S
authors.lastname: Reynard
authors.forename: Catherine
authors.initials: C
authors.lastname: Barbey
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cerottini
authors.forename: Serge
authors.initials: S
authors.lastname: Leyvraz
authors.forename: Clemencia
authors.initials: C
authors.lastname: Pinilla
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
mesh_terms: D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D022223:Vaccines, Subunit