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

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Serval ID
serval:BIB_943F39FA15D7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues.
Journal
International immunology
Author(s)
Valmori D., Fonteneau J.F., Valitutti S., Gervois N., Dunbar R., Liénard D., Rimoldi D., Cerundolo V., Jotereau F., Cerottini J.C., Speiser D.E., Romero P.
ISSN
0953-8178
Publication state
Published
Issued date
1999
Peer-reviewed
Oui
Volume
11
Number
12
Pages
1971-80
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
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 tumor-reactive 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.
Keywords
Antigens, Neoplasm, Calcium, Cell Line, Cytokines, Cytotoxicity, Immunologic, Humans, Lymphocyte Activation, Melanoma, Neoplasm Proteins, Receptors, Antigen, T-Cell, T-Lymphocytes
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 12:14
Last modification date
25/09/2019 7:10
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