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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
Author(s) -
Kawashima Ichiro,
Tsai Van,
Southwood Scott,
Takesako Kazutoh,
Celis Esteban,
Sette Alessandro
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19981109)78:4<518::aid-ijc20>3.0.co;2-0
Subject(s) - ctl* , epitope , cytotoxic t cell , biology , antigen , population , human leukocyte antigen , cd8 , immunology , major histocompatibility complex , microbiology and biotechnology , in vitro , medicine , genetics , environmental health
The human melanocyte lineage‐specific antigen gp100 contains several epitopes recognized by cytotoxic T lymphocytes (CTL). However, most of the epitopes reported to date are HLA‐A2.1‐restricted. Despite the high frequency of HLA‐A2.1 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[9 87 ] and gp100[10 86 ] ) 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*1101, ‐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\[9 87 \], which bound to HLA‐A11 with high affinity, was capable of inducing specific CTLs that killed melanoma cells expressing gp100 and HLA‐A11 molecules. Our results indicate that the gp100\[9 87 \] peptide corresponds to a CTL epitope which may be restricted by either the HLA‐A3 or HLA‐A11 allele, emphasizing its utility for the design and development of epitope‐based therapies for melanoma. Int. J. Cancer, 78:518–524, 1998. © 1998 Wiley‐Liss, Inc.