title: Prediction and identification of HLA-A*0201-restricted epitopes from leukemia-associated protein MLAA-22 which elicit cytotoxic T lymphocytes.
abstract: Cytotoxic T lymphocytes (CTLs) play a critical role in the control of leukemia. However, few effective CTL epitopes have been identified to date yet. We previously reported that MLAA-22, a protein composed of 631 amino acid residues, is a novel acute myeloid leukemia (AML)-associated antigen. In the present study, ten high-score 9-mer peptides, which were selected from MLAA-22 by using ProPred1 and SYFPEITHI bioinformatics tools, were screened to identify HLA-A*0201-restricted-specific CTL epitopes. Monocyte-derived dendritic cells were generated in vitro to be used as antigen-presenting cells for the induction of CTLs. We found that peptide MLAA-22(379-387) (LLPNAIYKV) exhibited the highest binding affinity to HLA-A*0201 among all peptide candidates in the peptide-T2 binding assay. The percentage of positive T2 cells treated with MLAA-22(379-387) was about 96.3%, which is even higher than that of the positive control peptide CML28(173-181) (95.1%). MLAA-22(379-387)-induced CTLs showed the most significant cytotoxic activity and apparent killing effects on the cell lines including THP-1 (human acute monocytic leukemia), A549, T2, U937, and MCF-7, and the specific lysis ratios were 83.8, 32.6, 64.4, 64.4, and 32.6%, respectively, when the effector to target ratio (E/T) was 20:1. Specific lysis (%) of MLAA1 was significantly increased (P < 0.05, P < 0.001, respectively) in THP-1 cell than those in other cancer cell lines and were 28.5, 67.8, and 83.8% at ratio 5:1, 10:1, and 20:1, respectively. Hence, MLAA-22(379-387) is a potential tumor-associated antigen target for AML immunotherapy.
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Ju
authors.initials: J
authors.lastname: Bai
authors.forename: Liufang
authors.initials: L
authors.lastname: Gu
authors.forename: Aili
authors.initials: A
authors.lastname: He
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
authors.forename: Pengyu
authors.initials: P
authors.lastname: Zhang
authors.forename: Wanggang
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D005544:Forecasting; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen