Skip to Main content Skip to Navigation
Journal articles

Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues

Abstract : Many mechanisms have been proposed to explain why immune responses against human tumor antigens are generally ineffective. For example, tumor cells have been shown to develop active immune evasion mechanisms. Another possibility is that tumor antigens are unable to optimally stimulate tumor-specific T cells. In this study we have used HLA-A2/Melan-A peptide tetramers to directly isolate antigen-specific CD8 ⍣ T cells from tumor-infiltrated lymph nodes. This allowed us to quantify the activation requirements of a representative polyclonal yet monospecific tumorreactive T cell population. The results obtained from quantitative assays of intracellular Ca 2⍣ mobilization, TCR down-regulation, cytokine production and induction of effector cell differentiation indicate that the naturally produced Melan-A peptides are weak agonists and are clearly suboptimal for T cell activation. In contrast, optimal T cell activation was obtained by stimulation with recently defined peptide analogues. These findings provide a molecular basis for the low immunogenicity of tumor cells and suggest that patient immunization with full agonist peptide analogues may be essential for stimulation and maintenance of anti-tumor T cell responses in vivo.
Document type :
Journal articles
Complete list of metadata
Contributor : Nadine GERVOIS Connect in order to contact the contributor
Submitted on : Monday, September 20, 2021 - 2:47:32 PM
Last modification on : Wednesday, January 12, 2022 - 2:44:02 PM
Long-term archiving on: : Tuesday, December 21, 2021 - 6:54:21 PM


 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document




Danila Valmori, Jean-Francois Fonteneau, Salvatore Valitutti, Nadine Gervois, Rod Dunbar, et al.. Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues. International Immunology, Oxford University Press (OUP), 1999, 11 (12), pp.1971-1980. ⟨10.1093/intimm/11.12.1971⟩. ⟨inserm-03349352⟩



Record views