PMID- 12394191 OWN - NLM STAT- MEDLINE DCOM- 20030501 LR - 20191025 IS - 0960-8931 (Print) IS - 0960-8931 (Linking) VI - 12 IP - 5 DP - 2002 Oct TI - Cytotoxic T-lymphocyte responses in melanoma through in vitro stimulation with the Melan-A peptide analogue A27L: a qualitative analysis. PG - 491-8 AB - 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. FAU - Palermo, B AU - Palermo B AD - Experimental Immunology, IRCCS Maugeri Foundation, Pavia, Italy. FAU - Campanelli, R AU - Campanelli R FAU - Garbelli, S AU - Garbelli S FAU - Mantovani, S AU - Mantovani S FAU - Robustelli Della Cuna, G AU - Robustelli Della Cuna G FAU - Necker, A AU - Necker A FAU - Manganoni, A M AU - Manganoni AM FAU - Carella, G AU - Carella G FAU - Rivoltini, L AU - Rivoltini L FAU - Lantelme, E AU - Lantelme E FAU - Giachino, C AU - Giachino C LA - eng PT - Journal Article PL - England TA - Melanoma Res JT - Melanoma research JID - 9109623 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (HLA Antigens) RN - 0 (MART-1 Antigen) RN - 0 (MLANA protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Peptides) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - Antibody Affinity MH - Antigens, Neoplasm MH - Cancer Vaccines/pharmacology MH - Dose-Response Relationship, Drug MH - Flow Cytometry MH - HLA Antigens/metabolism MH - Humans MH - MART-1 Antigen MH - Melanoma/immunology/*therapy MH - Neoplasm Proteins/*chemistry/genetics/*pharmacology MH - Peptides/chemistry/*pharmacology MH - Protein Binding MH - Receptors, Antigen, T-Cell/metabolism MH - T-Lymphocytes, Cytotoxic/*cytology/metabolism EDAT- 2002/10/24 04:00 MHDA- 2003/05/02 05:00 CRDT- 2002/10/24 04:00 PHST- 2002/10/24 04:00 [pubmed] PHST- 2003/05/02 05:00 [medline] PHST- 2002/10/24 04:00 [entrez] AID - 10.1097/00008390-200209000-00011 [doi] PST - ppublish SO - Melanoma Res. 2002 Oct;12(5):491-8. doi: 10.1097/00008390-200209000-00011.