title: TCR hypervariable regions expressed by T cells that respond to effective tumor vaccines.
abstract: A major goal of immunotherapy for cancer is the activation of T cell responses against tumor-associated antigens (TAAs). One important strategy for improving antitumor immunity is vaccination with peptide variants of TAAs. Understanding the mechanisms underlying the expansion of T cells that respond to the native tumor antigen is an important step in developing effective peptide-variant vaccines. Using an immunogenic mouse colon cancer model, we compare the binding properties and the TCR genes expressed by T cells elicited by peptide variants that elicit variable antitumor immunity directly ex vivo. The steady-state affinity of the natural tumor antigen for the T cells responding to effective peptide vaccines was higher relative to ineffective peptides, consistent with their improved function. Ex vivo analysis showed that T cells responding to the effective peptides expressed a CDR3β motif, which was also shared by T cells responding to the natural antigen and not those responding to the less effective peptide vaccines. Importantly, these data demonstrate that peptide vaccines can expand T cells that naturally respond to tumor antigens, resulting in more effective antitumor immunity. Future immunotherapies may require similar stringent analysis of the responding T cells to select optimal peptides as vaccine candidates.
authors.affiliation: Integrated Department of Immunology, School of Medicine, University of Colorado Denver, 1400 Jackson Street, Room K511, Denver, CO 80206, USA.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Jordan
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Buhrman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprague
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Moore
authors.forename: Dexiang
authors.initials: D
authors.lastname: Gao
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.forename: Jill E
authors.initials: JE
authors.lastname: Slansky
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology; D022801:Complementarity Determining Regions / Q000276:immunology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell; D022223:Vaccines, Subunit