Cytotoxic T-lymphocyte responses in melanoma through in vitro stimulation with the Melan-A peptide analogue A27L: A qualitative analysis

B. Palermo, R. Campanelli, S. Garbelli, S. Mantovani, G. Robustelli Della Cuna, A. Necker, A. M. Manganoni, G. Carella, L. Rivoltini, E. Lantelme, C. Giachino

Research output: Contribution to journalArticlepeer-review

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 in vitro 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.

Original languageEnglish
Pages (from-to)491-498
Number of pages8
JournalMelanoma Research
Volume12
Issue number5
DOIs
Publication statusPublished - Sep 2002

Keywords

  • Cancer vaccine
  • Cytotoxic T-lymphocyte
  • HLA tetramer
  • Melan-A/MART-1
  • Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Dermatology

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