Identification of antigenic epitopes recognized by Mac-2 binding protein-specific cytotoxic T lymphocytes for use in cancer immunotherapy.
We have previously reported that 90K/Mac-2 binding protein (M2BP) was highly expressed in lung cancer and that M2BP-specific immunity was observed in many of cancer patients. In this study, we analyzed the ability of 11 M2BP-derived oligopeptides with an HLA-A*0201-binding motif to induce M2BP-specific cytotoxic T lymphocytes (CTL) from peripheral blood lymphocytes of normal donors by in vitro stimulation. One of the CTLs that were induced using M2BP216-224 (RIDITLSSV) produced interferon-gamma in response to HLA-A2-positive T2 cells pulsed with the same peptide and lysed MDA-MB-231 cells expressing both M2BP and HLA-A2. The cytolytic activities were blocked by antibodies against HLA class I or CD8. These findings suggest that M2BP216-224 is naturally processed from the native M2BP in cancer cells and recognized by M2BP-specific CTLs in an HLA-A2 restriction. We first identified M2BP-derived CTL epitopes that may be useful as a target antigenic epitope in clinical immunotherapy of cancer.
Ozaki
Yoshitomo
Y
Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
Kontani
Keiichi
K
Teramoto
Koji
K
Fujita
Takuya
T
Tezuka
Noriaki
N
Sawai
Satoru
S
Watanabe
Hiroyoshi
H
Fujino
Shozo
S
Asai
Tohru
T
Ohkubo
Iwao
I
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D014408:Biomarkers, Tumor; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D016326:Extracellular Matrix Proteins
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D015234:HLA-A Antigens; D007371:Interferon-gamma; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins