A polyclonal anti-vaccine CD4 T cell response detected with HLA-DP4 multimers in a melanoma patient vaccinated with MAGE-3.DP4-peptide-pulsed dendritic cells.

Abstract

During the last few years, HLA class I tetramers have been successfully used to demonstrate anti-vaccine CD8 CTL proliferation in cancer patients vaccinated with tumor antigens. Frequencies of CTL as low as 10(-6) among CD8 cells were observed even in patients showing tumor regression. Little is known about the role of tumor-antigen-specific CD4 T cells in the context of these anti-vaccine responses. Therefore, we developed a very sensitive approach using fluorescent class-II-peptide multimers to detect antigen-specific CD4 T cells in vaccinated cancer patients. We produced HLA-DP4 multimers loaded with the MAGE-3(243-258) peptide and used them to stain ex vivo PBL from melanoma patients injected with dendritic cells pulsed with several class I and class II tumor antigenic peptides, including the MAGE-3(243-258) peptide. The multimer(+) CD4 T cells were sorted and amplified in clonal conditions; specificity was assessed by their ability to secrete IFN-gamma upon contact with the MAGE-3 antigen. We detected frequencies of about 1x10(-6) anti-MAGE-3.DP4 cells among CD4 cells. A detailed analysis of one patient showed an anti-MAGE-3.DP4 CD4 T cell amplification of at least 3000-fold upon immunization. TCR analysis of the clones from this patient demonstrated a polyclonal response against the MAGE-3 peptide.

• Authors: Yi Zhang, Nicolina Renkvist, Zhaojun Sun, Beatrice Schuler-Thurner, Nicolas Glaichenhaus, Gerold Schuler, Thierry Boon, Pierre van der Bruggen, Didier Colau
• Journal: European journal of immunology (Eur J Immunol) Vol. 35 Issue 4 Pg. 1066-75 (Apr 2005) ISSN: 0014-2980 [Print] Germany
• PMID: 15756643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neoplasm
• Antigens, Neoplasm
• Cancer Vaccines
• Epitopes, T-Lymphocyte
• HLA-DP Antigens
• HLA-DP beta-Chains
• HLA-DPw4 antigen
• MAGEA3 protein, human
• Neoplasm Proteins
• Peptide Fragments
• Biotin

Topics

• Antibodies, Neoplasm (immunology)
• Antigen Presentation
• Antigens, Neoplasm (immunology, metabolism)
• Biotin
• CD4-Positive T-Lymphocytes (immunology)
• Cancer Vaccines
• Dendritic Cells (immunology, transplantation)
• Epitopes, T-Lymphocyte (immunology)
• HLA-DP Antigens (immunology, metabolism)
• HLA-DP beta-Chains
• Humans
• Immunotherapy, Adoptive
• Melanoma (immunology, therapy)
• Neoplasm Proteins (immunology, metabolism)
• Peptide Fragments (immunology, metabolism)
• Vaccination