CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences

Clin Cancer Res. 2001 Mar;7(3 Suppl):766s-772s.


We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1. In the present study, we have analyzed in detail the relative antigenicity and in vitro immunogenicity of natural and modified NY-ESO-1 peptide sequences. The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients. In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently. In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level. Among natural peptides, NY-ESO-1 157-165 and NY-ESO-1 157-167 exhibited good in vitro immunogenicity, whereas peptide NY-ESO-1 155-163 was poorly immunogenic. The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions. The findings reported here have significant implications for the formulation of NY-ESO-1-based vaccines as well as for the monitoring of either natural or vaccine-induced NY-ESO-1-specific CTL responses in cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / metabolism*
  • Antigens, Neoplasm*
  • Binding, Competitive
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Separation
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • HLA-A2 Antigen / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Melanoma / metabolism
  • Membrane Proteins*
  • Microscopy, Fluorescence
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Binding
  • Proteins / metabolism*
  • Tumor Cells, Cultured


  • Antigens
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • HLA-A2 Antigen
  • Membrane Proteins
  • Peptides
  • Proteins
  • Interferon-gamma