PMID- 22074997 OWN - NLM STAT- MEDLINE DCOM- 20120518 LR - 20211021 IS - 1879-1166 (Electronic) IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 73 IP - 1 DP - 2012 Jan TI - Identification of HLA-A24-restricted CD8(+) cytotoxic T-cell epitopes derived from mammaglobin-A, a human breast cancer-associated antigen. PG - 11-6 LID - 10.1016/j.humimm.2011.10.017 [doi] AB - Human breast cancer-associated antigen, mammaglobin-A (Mam-A), potentially offers a novel therapeutic target as a breast cancer vaccine. In this study, we define the CD8(+) cytotoxic T lymphocyte (CTL) response to Mam-A-derived candidate epitopes presented in the context of HLA-A24 (A*2402). HLA-A24 has a frequency of 72% in Japanese, 27% in Asian Indian, and 18% in Caucasian populations. Using a human leukocyte antigen (HLA)-binding prediction algorithm we identified 7 HLA-A24-restricted Mam-A-derived candidate epitopes (MAA24.1-7). Membrane stabilization studies with TAP-deficient T2 cells transfected with HLA-A2402 (T2.A24) indicated that MAA24.2 (CYAGSGCPL) and MAA24.4 (ETLSNVEVF) have the highest HLA-A24 binding affinity. Further, 2 CD8(+) CTL cell lines generated in vitro against T2.A24 cells individually loaded with Mam-A-derived candidate epitopes demonstrated significant cytotoxic activity against MAA24.2 and MAA24.4. In addition, the same CD8(+) CTL lines lysed the HLA-A24(+)/Mam-A(+) stable transfected human breast cancer cell lines AU565 and MDA-MB-361. However, these CTLs had no cytotoxicity against HLA-A24(-)/Mam-A(+) and HLA-A24(+)/Mam-A(-) breast cancer cell lines. In summary, our results define HLA-A24-restricted, Mam-A-derived, CD8(+) CTL epitopes that can potentially be employed for Mam-A-based breast cancer vaccine therapy to breast cancer patients with HLA-A24 phenotype. CI - Copyright (c) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. FAU - Tiriveedhi, Venkataswarup AU - Tiriveedhi V AD - Department of Surgery, Washington University School of Medicine, Saint Louis, Missouri 63110, USA. FAU - Sarma, Nayan J AU - Sarma NJ FAU - Subramanian, Vijay AU - Subramanian V FAU - Fleming, Timothy P AU - Fleming TP FAU - Gillanders, William E AU - Gillanders WE FAU - Mohanakumar, Thallachallour AU - Mohanakumar T LA - eng GR - P30 CA091842/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20111023 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (CD8 Antigens) RN - 0 (Cancer Vaccines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A24 Antigen) RN - 0 (Mammaglobin A) SB - IM MH - Amino Acid Sequence MH - Binding, Competitive/immunology MH - Breast Neoplasms/genetics/*immunology/pathology MH - CD8 Antigens/immunology/metabolism MH - Cancer Vaccines/genetics/immunology/metabolism MH - Cell Line, Tumor MH - Cells, Cultured MH - Cytotoxicity, Immunologic/immunology MH - Epitope Mapping MH - Epitopes, T-Lymphocyte/genetics/*immunology/metabolism MH - Female MH - HLA-A24 Antigen/genetics/*immunology/metabolism MH - Humans MH - Mammaglobin A/genetics/*immunology MH - Protein Binding/immunology MH - T-Lymphocytes, Cytotoxic/*immunology/metabolism MH - Transfection PMC - PMC3674634 MID - NIHMS464460 EDAT- 2011/11/15 06:00 MHDA- 2012/05/19 06:00 PMCR- 2013/06/06 CRDT- 2011/11/15 06:00 PHST- 2011/07/29 00:00 [received] PHST- 2011/07/29 00:00 [revised] PHST- 2011/10/12 00:00 [accepted] PHST- 2011/11/15 06:00 [entrez] PHST- 2011/11/15 06:00 [pubmed] PHST- 2012/05/19 06:00 [medline] PHST- 2013/06/06 00:00 [pmc-release] AID - S0198-8859(11)00563-5 [pii] AID - 10.1016/j.humimm.2011.10.017 [doi] PST - ppublish SO - Hum Immunol. 2012 Jan;73(1):11-6. doi: 10.1016/j.humimm.2011.10.017. Epub 2011 Oct 23.