Identification of human leucocyte antigen (HLA)‐A*0201‐restricted cytotoxic T lymphocyte epitopes derived from HLA‐DOβ as a novel target for multiple myeloma. (30th August 2013)

• Record Type: Journal Article
• Authors: Kang, Yoon Joong; Zeng, Wanyong; Song, Weihua; Reinhold, Bruce; Choi, Jaewon; Brusic, Vladimir; Yamashita, Takuto; Munshi, Aditya; Li, Cheng; Minvielle, Stephane; Anderson, Kenneth C.; Munshi, Nikhil; Reinherz, Ellis L.; Sasada, Tetsuro
• Is Part Of: British journal of haematology. Volume 163:Number 3(2013:Nov.)
• Page Start: 343
• Page End: 351
• Publication Date: 2013-08-30
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12544
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12544-abs-0001"> <title>Summary</title> <p>Despite the recent development of effective therapeutic agents against multiple myeloma (MM), new therapeutic approaches, including immunotherapies, remain to be developed. Here we identified novel human leucocyte antigen (HLA)‐A*0201 (HLA‐A2)‐restricted cytotoxic T lymphocyte (CTL) epitopes from a B cell specific molecule HLA‐DOβ (DOB) as a potential target for MM. By DNA microarray analysis, the <italic>HLA‐DOB</italic> expression in MM cells was significantly higher than that in normal plasma cells. Twenty‐five peptides were predicted to bind to HLA‐A2 from the amino acid sequence of HLA‐DOB. When screened for the immunogenicity in HLA‐A2‐transgenic mice immunized with <italic>HLA‐DOB</italic> cDNA, 4 peptides were substantially immunogenic. By mass spectrometry analysis of peptides eluted from HLA‐A2‐immunoprecipitates of MM cell lines, only two epitopes, HLA‐DOB<sub>232–240</sub> (FLLGLIFLL) and HLA‐DOB<sub>185–193</sub> (VMLEMTPEL), were confirmed for their physical presence on cell surface. When healthy donor blood was repeatedly stimulated <italic>in vitro</italic> with these two peptides and assessed by antigen‐specific γ‐interferon secretion, HLA‐DOB<sub>232–240</sub> was more immunogenic than HLA‐DOB<sub>185–193</sub>. Additionally, the HLA‐DOB<sub>232–240</sub>‐specific CTLs, but not the HLA‐DOB<sub>185–193</sub>‐specific CTLs, displayed an major histocompatibility complex class I‐restricted reactivity against MM cell lines expressing both HLA‐A2 and HLA‐DOB. Taken together, based on the physical presence on tumour cell surface and high immunogenicity, HLA‐DOB<sub>232–240</sub> might be useful for developing a novel immunotherapy against MM.</p> </abstract>