Identification of CD4+ T cell epitopes from NY-ESO-1 presented by HLA-DR molecules

J Immunol. 2000 Jul 15;165(2):1153-9. doi: 10.4049/jimmunol.165.2.1153.

Abstract

In previous studies, the shared cancer-testis Ag, NY-ESO-1, was demonstrated to be recognized by both Abs and CD8+ T cells. Gene expression of NY-ESO-1 was detected in many tumor types, including melanoma, breast, and lung cancers, but was not found in normal tissues, with the exception of testis. In this study, we describe the identification of MHC class II-restricted T cell epitopes from NY-ESO-1. Candidate CD4+ T cell peptides were first identified using HLA-DR4 transgenic mice immunized with the NY-ESO-1 protein. NY-ESO-1-specific CD4+ T cells were then generated from PBMC of a patient with melanoma stimulated with the candidate peptides in vitro. These CD4+ T cells recognized NY-ESO-1 peptides or protein pulsed on HLA-DR4+ EBV B cells, and also recognized tumor cells expressing HLA-DR4 and NY-ESO-1. A 10-mer peptide (VLLKEFTVSG) was recognized by CD4+ T cells. These studies provide new opportunities for developing more effective vaccine strategies by using tumor-specific CD4+ T cells. This approach may be applicable to the identification of CD4+ T cell epitopes from many known tumor Ags recognized by CD8+ T cells.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Neoplasm / analysis
  • Antigen Presentation* / genetics
  • Antigens, Neoplasm / metabolism*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • Female
  • Genetic Vectors / immunology
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / metabolism*
  • HLA-DR4 Antigen / genetics
  • HLA-DR4 Antigen / metabolism
  • Humans
  • Immune Sera / analysis
  • Lymphocyte Activation
  • Melanoma / immunology
  • Melanoma / metabolism
  • Melanoma / secondary
  • Membrane Proteins*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / immunology*
  • Proteins / metabolism*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Epitopes, T-Lymphocyte
  • HLA-DR Antigens
  • HLA-DR4 Antigen
  • Immune Sera
  • Membrane Proteins
  • Peptide Fragments
  • Proteins
  • Recombinant Proteins