Cross-reactive CD4+ T cells against one immunodominant tumor-derived epitope in melanoma patients

J Immunol. 2007 Dec 1;179(11):7932-40. doi: 10.4049/jimmunol.179.11.7932.


TCRs exhibit a high degree of specificity but may also recognize multiple and distinct peptide-MHC complexes, illustrating the so-called cross-reactivity of TCR-peptide-MHC recognition. In this study, we report the first evidence of CD4(+) T cells recognizing the same tumor peptide-epitope from NY-ESO-1, in the context of multiple HLA-DR and HLA-DP molecules. These cross-reactive CD4(+) T cells recognized not only autologous but also allogenic dendritic cells previously loaded with the relevant protein (i.e., the normally processed and presented epitope). Using clonotypic real-time RT-PCR, we have detected low frequencies of CD4(+) T cells expressing one cross-reactive TCR from circulating CD4(+) T cells of patients with stage IV melanoma either spontaneously or after immunization but not in normal donors. The maintenance of cross-reactive tumor Ag-specific CD4(+) T cells in PBLs of cancer patients required the presence of tumor Ag/epitope in the context of the MHC molecule used to prime the Ag-specific CD4(+) T cells. Our findings have significant implications for the optimization of TCR gene transfer immunotherapies widely applicable to cancer patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Antibody Reactions
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cell Proliferation
  • HLA-DR Antigens / immunology
  • Humans
  • Immunodominant Epitopes / immunology*
  • Major Histocompatibility Complex / immunology
  • Melanoma / blood
  • Melanoma / genetics
  • Melanoma / immunology*
  • Membrane Proteins / biosynthesis
  • Neoplasm Proteins / immunology
  • Neoplasm Staging
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Recombinant Proteins / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transduction, Genetic


  • Antigens, Neoplasm
  • CTAG1B protein, human
  • HLA-DR Antigens
  • Immunodominant Epitopes
  • Membrane Proteins
  • Neoplasm Proteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins