Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen
- 11 March 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (10), 3849-3854
- https://doi.org/10.1073/pnas.0800080105
Abstract
Human cancer vaccines are often prepared with altered “analog” or “heteroclitic” antigens that have been optimized for HLA class I binding, resulting in enhanced immunogenicity. Here, we take advantage of CpG oligodeoxynucleotides as powerful vaccine adjuvants and demonstrate the induction of high T cell frequencies in melanoma patients, despite the use of natural (unmodified) tumor antigenic peptide. Compared with vaccination with analog peptide, natural peptide induced T cell frequencies that were approximately twofold lower. However, T cells showed superior tumor reactivity because of (i) increased functional avidity for natural antigen and (ii) enhancement of T cell activation and effector function. Thus, novel vaccine formulations comprising potent immune stimulators may allow to circumvent the need for modified antigens and can induce highly functional T cells with precise antigen specificity.Keywords
This publication has 43 references indexed in Scilit:
- Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivoBlood, 2006
- Duration of the initial TCR stimulus controls the magnitude but not functionality of the CD8+ T cell responseThe Journal of Experimental Medicine, 2006
- Translating Innate Immunity into Immunological Memory: Implications for Vaccine DevelopmentCell, 2006
- Diversity and Recognition Efficiency of T Cell Responses to CancerPLoS Medicine, 2004
- Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cellsSeminars in Cancer Biology, 2003
- Tumour immunologyCurrent Opinion in Immunology, 2003
- Adjuvant Immunization of HLA-A2–Positive Melanoma Patients With a Modified gp100 Peptide Induces Peptide-Specific CD8+T-Cell ResponsesJournal of Clinical Oncology, 2003
- Degeneracy of Antigen Recognition as the Molecular Basis for the High Frequency of Naive A2/Melan-A Peptide Multimer+ CD8+ T Cells in HumansThe Journal of Experimental Medicine, 2002
- Estimating the Precursor Frequency of Naive Antigen-specific CD8 T CellsThe Journal of Experimental Medicine, 2002
- Phenotypic Analysis of Antigen-Specific T LymphocytesScience, 1996