Tumor-reactive T helper lymphocytes recognize a promiscuous MAGE-A3 epitope presented by various major histocompatibility complex class II alleles.
The development of effective T cell-based immunotherapy for cancer requires the identification of antigens capable of inducing both CTL and T helper immune responses. Although CTLs will participate in the antitumor response mainly by exerting their lytic activity on the tumor cells, helper T lymphocytes will be critical for the induction and maintenance of the CTLs. Thus, effective subunit therapeutic vaccines should include both CTL and T helper epitopes from antigens expressed on the tumor cells. The product of the MAGE-A3 gene is an attractive candidate for tumor immunotherapy because it is expressed in the majority of melanomas and in a great proportion of other solid tumors. Although numerous CTL epitopes for the MAGE-A3 antigen have been reported, only a few have been described for helper T cells. Here we show that a synthetic peptide derived from the MAGE-A3 sequence (MAGE-A3(146-160)) was effective in inducing in vitro T helper responses in the context of HLA-DR4 and HLA-DR7 alleles. Most significantly, the peptide-reactive helper T lymphocytes were capable of recognizing various forms of MAGE-A3 antigen (tumor cell lysates, dead/apoptotic tumor cells, or recombinant MAGE-A3 protein), indicating that the T-cell epitope represented by peptide MAGE-A3(146-160) is naturally processed by antigen-presenting cells. These studies are relevant for the design of multi-epitope vaccines for treating MAGE-A3-expressing tumors through the simultaneous stimulation of CTL and T helper lymphocytes.
Kobayashi
H
H
Department of Immunology, Mayo Graduate School, and Mayo Cancer Center, Mayo Clinic, Rochester, Minnesota 55905, USA.
Song
Y
Y
Hoon
D S
DS
Appella
E
E
Celis
E
E
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015804:HLA-DR4 Antigen / Q000276:immunology*; D015809:HLA-DR7 Antigen / Q000276:immunology*; D006801:Humans; D007739:L Cells; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D051379:Mice; D009363:Neoplasm Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015804:HLA-DR4 Antigen; D015809:HLA-DR7 Antigen; C072013:MAGEA3 protein, human; C489519:Mageb3 protein, mouse; D009363:Neoplasm Proteins