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.
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.
Zhang
Yi
Y
Ludwig Institute for Cancer Research and Cellular Genetics Unit, Université de Louvain, Brussels, Belgium.
Renkvist
Nicolina
N
Sun
Zhaojun
Z
Schuler-Thurner
Beatrice
B
Glaichenhaus
Nicolas
N
Schuler
Gerold
G
Boon
Thierry
T
van der Bruggen
Pierre
P
Colau
Didier
D
D000912:Antibodies, Neoplasm / Q000276:immunology; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D001710:Biotin; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006682:HLA-DP Antigens / Q000276:immunology* / Q000378:metabolism; D059868:HLA-DP beta-Chains; D006801:Humans; D016219:Immunotherapy, Adoptive; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C056284:HLA-DPw4 antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D001710:Biotin