Identification of DR9-restricted XAGE antigen on lung adenocarcinoma recognized by autologous CD4 T-cells.
We previously demonstrated a dominant IgG response against XAGE-1b antigen in a lung cancer patient by serological analysis of antigens by recombinant expression cloning (SEREX) analysis using a cDNA library from the autologous OU-LU-6 tumor cell line. In this study, we investigated recognition of XAGE-1b on OU-LU-6 tumor by the patient CD4-expressing tumor-infiltrating lymphocytes (CD4 TIL). The response of CD4 TIL obtained from malignant pleural effusion was determined against autologous OU-LU-6 tumor cells and XAGE-1b mRNA-transfected PHA-stimulated CD4 T-cells (T-APC) from healthy individuals sharing HLA-DR with the patient by performing IFNgamma secretion and ELISPOT assays. The patient CD4 TIL recognized OU-LU-6 in an HLA-DR-restricted manner and XAGE-1b mRNA-transfected T-APC derived from DRB1 *0901-sharing healthy donor (HD)1 and HD2, but not DRB1 *1101-sharing HD3 or HD4. Epitope analysis using 17 18-mer peptides with 12 overlapping amino acids revealed that the CD4 TIL recognized XAGE-1b 33-49. The findings suggest that the patient CD4 T-cells recognized the XAGE-1b 33-49-related epitope on autologous OU-LU-6 tumor cells in a manner restricted by DR *0901.
Shimono
Michihide
M
Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Uenaka
Akiko
A
Noguchi
Yuji
Y
Sato
Shuichiro
S
Okumura
Hideo
H
Nakagawa
Kazuhiko
K
Kiura
Katsuyuki
K
Tanimoto
Mitsune
M
Nakayama
Eiichi
E
D000230:Adenocarcinoma / Q000737:chemistry / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data
D000951:Antigens, Neoplasm; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C487381:HLA-DRB1*09:01 antigen; C413656:XAGE1A protein, human