TY - JOUR
T1 - Cytotoxic T-lymphocyte responses in melanoma through in vitro stimulation with the Melan-A peptide analogue A27L
T2 - A qualitative analysis
AU - Palermo, B.
AU - Campanelli, R.
AU - Garbelli, S.
AU - Mantovani, S.
AU - Della Cuna, G. Robustelli
AU - Necker, A.
AU - Manganoni, A. M.
AU - Carella, G.
AU - Rivoltini, L.
AU - Lantelme, E.
AU - Giachino, C.
PY - 2002/9
Y1 - 2002/9
N2 - 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.
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 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.
KW - Cancer vaccine
KW - Cytotoxic T-lymphocyte
KW - HLA tetramer
KW - Melan-A/MART-1
KW - Melanoma
UR - http://www.scopus.com/inward/record.url?scp=0036752157&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036752157&partnerID=8YFLogxK
U2 - 10.1097/00008390-200209000-00011
DO - 10.1097/00008390-200209000-00011
M3 - Article
C2 - 12394191
AN - SCOPUS:0036752157
VL - 12
SP - 491
EP - 498
JO - Melanoma Research
JF - Melanoma Research
SN - 0960-8931
IS - 5
ER -