This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alisa, A. Articles by Behboudi, S. Search for Related Content PubMed PubMed Citation Articles by Alisa, A. Articles by Behboudi, S.

Analysis of CD4⁺ T-Cell Responses to a Novel -Fetoprotein-Derived Epitope in Hepatocellular Carcinoma Patients

Authors' Affiliations: ¹ Institute of Hepatology, University College London; ² Liver Unit, Cromwell Hospital; ³ Department of Histocompatibility and Immunogenetics, NBS-London and SE Zone, North London Blood Centre; ⁴ Department of Immunology and Molecular Pathology, Royal Free and University College Medical School, University College London, London, United Kingdom; and ⁵ Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom

Requests for reprints: Shahriar Behboudi, Institute of Hepatology, University College London, 69-75 Chenies Mews, London, WC1E 6HX, United Kingdom. Phone: 44-20-7679-6517; Fax: 44-20-7380-0405; E-mail: s.behboudi{at}ucl.ac.uk.

Purpose: -Fetoprotein (AFP) is a tumor-associated antigen in hepatocellular carcinoma and is a target for the development of cancer vaccine. Four immunodominant AFP-derived HLA-A*0201-restricted peptides have been identified and the administration of these peptides with an adjuvant has stimulated AFP-specific CTL responses in hepatocellular carcinoma patients. However, no AFP-derived CD4 T-cell epitope has yet been reported and the status of AFP-specific CD4⁺ T-cell responses in hepatocellular carcinoma patients is not fully understood. The aim of this study was to analyze naturally occurring CD4⁺ T-cell responses to AFP.

Experimental Design: We analyzed the ability of CD4⁺ T cells to recognize an HLA-DR-restricted AFP-derived epitope in 41 hepatocellular carcinoma patients and 24 non-hepatocellular carcinoma control patients using intracellular cytokine assays for IFN-.

Results: Here, for the first time, we report the identification of an AFP-derived CD4⁺ T-cell epitope that is recognized by circulating lymphocytes from hepatocellular carcinoma patients in association with HLA-DR. The absence of detectable responses in healthy donors and patients with chronic liver disease suggests that AFP-specific CD4⁺ T cells in the responder patients had been previously expanded in vivo in response to the tumor. The anti-AFP CD4⁺ T-cell response was only detected in hepatocellular carcinoma patients with normal or mildly elevated serum AFP levels who were in the early stage of disease.

Conclusion: Our data will be instrumental in the development of cancer vaccine using AFP-derived immunogens.

This article has been cited by other articles:

				A. Alisa, S. Boswell, A. A. Pathan, L. Ayaru, R. Williams, and S. Behboudi Human CD4+ T Cells Recognize an Epitope within {alpha}-Fetoprotein Sequence and Develop into TGF-{beta}-Producing CD4+ T Cells J. Immunol., April 1, 2008; 180(7): 5109 - 5117. [Abstract] [Full Text] [PDF]

				L. Ayaru, S. P. Pereira, A. Alisa, A. A. Pathan, R. Williams, B. Davidson, A. K. Burroughs, T. Meyer, and S. Behboudi Unmasking of {alpha}-Fetoprotein-Specific CD4+ T Cell Responses in Hepatocellular Carcinoma Patients Undergoing Embolization J. Immunol., February 1, 2007; 178(3): 1914 - 1922. [Abstract] [Full Text] [PDF]