title: Cytotoxic T-lymphocyte responses in melanoma through in vitro stimulation with the Melan-A peptide analogue A27L: a qualitative analysis.
abstract: Modifications in tumour antigen-derived epitopes that stabilize the major histocompatibility complex (MHC)-peptide complex result in enhanced stimulatory capacity and improved immunogenicity of the altered peptide. These epitope analogues are attractive candidates for the development of peptide-based vaccine trials. Any modification, however, in tumour antigens may induce T-cell responses that could either fail to react against the naturally occurring peptides or represent only a subset of the total antigen-specific repertoire. In the present study, we performed a critical analysis of the ability of cytotoxic T-lymphocyte (CTL) clones, derived from two melanoma patients through stimulation with the A27L peptide analogue, to cross-react with the naturally processed Melan-A/MART-1 (Melan-A) peptides in terms of T-cell receptor (TCR) affinity, functional avidity and fine antigen specificity. We found that all the A27L-specific clones analysed possessed a very low avidity for the natural Melan-A peptides, and that their binding affinity for human leukocyte antigen (HLA) tetramers complexed with both the modified and the natural Melan-A peptides did not strictly correlate with their functional avidity. We also observed that these clones were able to cross-recognize both natural Melan-A peptides in one patient, but only one peptide in the second patient. We discuss the capability of the A27L peptide analogue to stimulate all the available Melan-A-specific repertoire.
authors.affiliation: Experimental Immunology, IRCCS Maugeri Foundation, Pavia, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Palermo
authors.forename: R
authors.initials: R
authors.lastname: Campanelli
authors.forename: S
authors.initials: S
authors.lastname: Garbelli
authors.forename: S
authors.initials: S
authors.lastname: Mantovani
authors.forename: G
authors.initials: G
authors.lastname: Robustelli Della Cuna
authors.forename: A
authors.initials: A
authors.lastname: Necker
authors.forename: A M
authors.initials: AM
authors.lastname: Manganoni
authors.forename: G
authors.initials: G
authors.lastname: Carella
authors.forename: L
authors.initials: L
authors.lastname: Rivoltini
authors.forename: E
authors.initials: E
authors.lastname: Lantelme
authors.forename: C
authors.initials: C
authors.lastname: Giachino
mesh_terms: D000915:Antibody Affinity; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006680:HLA Antigens; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell