title: Enhanced antigen-specific antitumor immunity with altered peptide ligands that stabilize the MHC-peptide-TCR complex.
abstract: T cell responsiveness to an epitope is affected both by its affinity for the presenting MHC molecule and the affinity of the MHC-peptide complex for TCR. One limitation of cancer immunotherapy is that natural tumor antigens elicit relatively weak T cell responses, in part because high-affinity T cells are rendered tolerant to these antigens. We report here that amino acid substitutions in a natural MHC class I-restricted tumor antigen that increase the stability of the MHC-peptide-TCR complex are significantly more potent as tumor vaccines. The improved immunity results from enhanced in vivo expansion of T cells specific for the natural tumor epitope. These results indicate peptides that stabilize the MHC-peptide-TCR complex may provide superior antitumor immunity through enhanced stimulation of specific T cells.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Slansky
authors.forename: F M
authors.initials: FM
authors.lastname: Rattis
authors.forename: L F
authors.initials: LF
authors.lastname: Boyd
authors.forename: T
authors.initials: T
authors.lastname: Fahmy
authors.forename: E M
authors.initials: EM
authors.lastname: Jaffee
authors.forename: J P
authors.initials: JP
authors.lastname: Schneck
authors.forename: D H
authors.initials: DH
authors.lastname: Margulies
authors.forename: D M
authors.initials: DM
authors.lastname: Pardoll
mesh_terms: D000409:Alanine / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D015179:Colorectal Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006183:H-2 Antigens / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008024:Ligands; D009842:Oligopeptides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D000409:Alanine