TY - JOUR
T1 - Identification of GP100-derived, melanoma-specific cytotoxic T- lymphocyte epitopes restricted by HLA-A3 supertype molecules by primary in vitro immunization with peptide-pulsed dendritic cells
AU - Kawashtma, Ichiro
AU - Tsai, Van
AU - Southwood, Scott
AU - Takesako, Kazutoh
AU - Celis, Esteban
AU - Sette, Alessandro
PY - 1998/11/2
Y1 - 1998/11/2
N2 - The human melanocyte lineage-specific antigen gp 100 contains several epitopes recognized by cytotoxic T lymphocytes (CTL). However, most of the epitopes reported to date are HLA-A2.I-restricted. Despite the high frequency of HLAA2.1 in melanoma patients, effective population coverage requires the identification of epitopes restricted by other frequent HLA alleles. Herein, HLA-A3 binding, gp100-derived synthetic peptides were tested for their capacity to elicit anti-melanoma CTL in vitro using CD8+ T cells from healthy donors as responders and peptide-pulsed autologous dendritic cells as antigen-presenting cells. Of 7 peptides tested, 2 (gp100[987] and gp100[1086]) induced CTLs that killed melanoma cell lines expressing HLA- A3 and gp100. Additional MHC-binding studies to various HLA molecules belonging to the HLA-A3 superfamily (HLA-A*II01, -A*3101, -A*3301 and - A*6801) were performed to determine whether these CTL epitopes could further increase potential population coverage. Further experiments indicated that the peptide gp100[987], which bound to HLA-AII with high affinity, was capable of inducing specific CTLs that killed melanoma cells expressing gp100 and HLA-AII molecules. Our results indicate that the gp100[987] peptide corresponds to a CTL epitope which may be restricted by either the HLA-A3 or HLA-AII allele, emphasizing its utility for the design and development of epitope-based therapies for melanoma.
AB - The human melanocyte lineage-specific antigen gp 100 contains several epitopes recognized by cytotoxic T lymphocytes (CTL). However, most of the epitopes reported to date are HLA-A2.I-restricted. Despite the high frequency of HLAA2.1 in melanoma patients, effective population coverage requires the identification of epitopes restricted by other frequent HLA alleles. Herein, HLA-A3 binding, gp100-derived synthetic peptides were tested for their capacity to elicit anti-melanoma CTL in vitro using CD8+ T cells from healthy donors as responders and peptide-pulsed autologous dendritic cells as antigen-presenting cells. Of 7 peptides tested, 2 (gp100[987] and gp100[1086]) induced CTLs that killed melanoma cell lines expressing HLA- A3 and gp100. Additional MHC-binding studies to various HLA molecules belonging to the HLA-A3 superfamily (HLA-A*II01, -A*3101, -A*3301 and - A*6801) were performed to determine whether these CTL epitopes could further increase potential population coverage. Further experiments indicated that the peptide gp100[987], which bound to HLA-AII with high affinity, was capable of inducing specific CTLs that killed melanoma cells expressing gp100 and HLA-AII molecules. Our results indicate that the gp100[987] peptide corresponds to a CTL epitope which may be restricted by either the HLA-A3 or HLA-AII allele, emphasizing its utility for the design and development of epitope-based therapies for melanoma.
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U2 - 10.1002/(SICI)1097-0215(19981109)78:4<518::AID-IJC20>3.0.CO;2-0
DO - 10.1002/(SICI)1097-0215(19981109)78:4<518::AID-IJC20>3.0.CO;2-0
M3 - Article
C2 - 9797143
AN - SCOPUS:0031755442
SN - 0020-7136
VL - 78
SP - 518
EP - 524
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -