title: In vivo evidence that peptide vaccination can induce HLA-DR-restricted CD4+ T cells reactive to a class I tumor peptide.
abstract: Vaccination with class I tumor peptides has been performed to induce tumor-reactive CD8(+) T cells in vivo. However, the kinds of immune responses that vaccination might elicit in patients are not fully understood. In this study we tried to elucidate the mechanisms by which vaccination of class I binding tumor peptides into an HLA-A2(+) lung cancer patient elicited dramatic amounts of IgG1 and IgG2 specific to a nonamer peptide, ubiquitin-conjugated enzyme variant Kua (UBE2V)(43-51). The UBE2V(43-51) peptide contains cysteine at the sixth position. HLA-DR-restricted and UBE2V(43-51) peptide-recognizing CD4(+) T cells were induced from postvaccination, but not from prevaccination, PBMCs of the cancer patient. In addition, a CD4(+) T cell line (UB-2) and its clone (UB-2.3), both of which recognize the UBE2V(43-51) peptide in the context of HLA-DRB1*0403 molecules, were successfully established from postvaccination PBMCs. The peptide vaccination increased the frequency of peptide-specific T cells, especially CD4(+) T cells. In contrast, mass spectrometric analysis revealed that the vaccinated UBE2V(43-51) peptide contained both monomeric and dimeric forms. Both forms, fractionated by reverse phase HPLC, were recognized by UB-2 and UB-2.3 cells. Recognition by these CD4(+) T cells was observed despite the addition of a reduction reagent or the fixation of APC. Overall, these results indicate that vaccination with class I tumor peptides can induce HLA-DR-restricted CD4(+) T cells in vivo and elicit humoral immune responses, and that a cysteine-containing peptide can be recognized by CD4(+) T cells not only as a monomer, but also as a dimer.
authors.affiliation: Department of Immunology, Kurume University School of Medicine, Fukuoka, Japan. haramamp@med.kurume-u.ac.jp
authors.forename: Mamoru
authors.initials: M
authors.lastname: Harada
authors.forename: Rumi
authors.initials: R
authors.lastname: Gohara
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.forename: Akira
authors.initials: A
authors.lastname: Muto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oda
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000368:Aged; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D002999:Clone Cells; D019281:Dimerization; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D018655:Lymphocyte Count; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D044763:Ubiquitin-Conjugating Enzymes / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D010446:Peptide Fragments; D014157:Transcription Factors; C471624:UBE2V1 protein, human; D044763:Ubiquitin-Conjugating Enzymes