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

Int J Cancer. 1998 Nov 9;78(4):518-24. doi: 10.1002/(sici)1097-0215(19981109)78:4<518::aid-ijc20>3.0.co;2-0.

Abstract

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.

MeSH terms

  • Cell Line
  • Cells, Cultured
  • Cross Reactions
  • Dendritic Cells / immunology*
  • Dose-Response Relationship, Immunologic
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-A Antigens / immunology
  • HLA-A11 Antigen
  • HLA-A3 Antigen / immunology*
  • Humans
  • Immunization
  • Membrane Glycoproteins / immunology*
  • Neoplasm Proteins / immunology*
  • Peptide Fragments / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • gp100 Melanoma Antigen

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A11 Antigen
  • HLA-A3 Antigen
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Peptide Fragments
  • gp100 Melanoma Antigen