Article Dans Une Revue Journal of Immunology Année : 2007

Cross-Reactive CD4+ T Cells against One Immunodominant Tumor-Derived Epitope in Melanoma Patients

Pavol Kudela
  • Fonction : Auteur
Bratislav Janjic
  • Fonction : Auteur
Julien Fourcade
  • Fonction : Auteur
Pedro Andrade
  • Fonction : Auteur
John Kirkwood
  • Fonction : Auteur
Talal El-Hefnawy
  • Fonction : Auteur
Massimo Amicosante
  • Fonction : Auteur
Bernard Maillere
  • Fonction : Auteur
Hassane Zarour
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-04667919 , version 1 (05-08-2024)

Identifiants

Citer

Pavol Kudela, Bratislav Janjic, Julien Fourcade, Florence Castelli, Pedro Andrade, et al.. Cross-Reactive CD4+ T Cells against One Immunodominant Tumor-Derived Epitope in Melanoma Patients. Journal of Immunology, 2007, 179 (11), pp.7932-7940. ⟨10.4049/jimmunol.179.11.7932⟩. ⟨hal-04667919⟩
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