Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues.
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...
| প্রধান লেখক: | , , , , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
1999
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| _version_ | 1826291876675715072 |
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| author | Valmori, D Fonteneau, J Valitutti, S Gervois, N Dunbar, R Liénard, D Rimoldi, D Cerundolo, V Jotereau, F Cerottini, J Speiser, D Romero, P |
| author_facet | Valmori, D Fonteneau, J Valitutti, S Gervois, N Dunbar, R Liénard, D Rimoldi, D Cerundolo, V Jotereau, F Cerottini, J Speiser, D Romero, P |
| author_sort | Valmori, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:06:04Z |
| format | Journal article |
| id | oxford-uuid:b2923fdc-1cdc-42ef-851d-1e0a007a81f5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:06:04Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:b2923fdc-1cdc-42ef-851d-1e0a007a81f52022-03-27T04:12:39ZOptimal activation of tumor-reactive T cells by selected antigenic peptide analogues.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b2923fdc-1cdc-42ef-851d-1e0a007a81f5EnglishSymplectic Elements at Oxford1999Valmori, DFonteneau, JValitutti, SGervois, NDunbar, RLiénard, DRimoldi, DCerundolo, VJotereau, FCerottini, JSpeiser, DRomero, PMany 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. |
| spellingShingle | Valmori, D Fonteneau, J Valitutti, S Gervois, N Dunbar, R Liénard, D Rimoldi, D Cerundolo, V Jotereau, F Cerottini, J Speiser, D Romero, P Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues. |
| title | Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues. |
| title_full | Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues. |
| title_fullStr | Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues. |
| title_full_unstemmed | Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues. |
| title_short | Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues. |
| title_sort | optimal activation of tumor reactive t cells by selected antigenic peptide analogues |
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