期刊
LEUKEMIA
卷 20, 期 6, 页码 1067-1072出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.leu.2404234
关键词
chronic myelogenous leukaemia; proteinase 3; peptide sequencing & MHC-ligands
Three of the most promising antigens for immunotherapy of chronic myelogenous leukaemia (CML) include the specific fusion-protein, Bcr/AbI, and the overexpressed proteins WT1 and Proteinase 3. The clinical significance of Proteinase 3 as a target in myelogenous leukaemias has been bolstered by detection of high frequencies of cytotoxic CD8+ lymphocytes specific for this antigen in patients undergoing immune therapies. Our investigation aimed to directly identify MHC-ligands derived from these antigens and presented on CML blasts by means of affinity-purification and mass spectrometric peptide-sequencing. Although no known or potential new epitopes were discovered for Bcr/AbI or WT1, a novel peptide from Proteinase 3 was detected among the more abundant MHC-ligands. Additionally, MHC-ligands derived from known immunogenic proteins overexpressed as a result of Bcr/AbI transformation were also identified. Our investigation is the second of only a small number of studies to identify a peptide from Proteinase 3 among the more abundant MHC-associated peptides and thus implies that peptides from this antigen are among the more abundantly presented of the known leukaemic antigens. Taken in conjunction with clinical observations of functional Proteinase 3 specific CTL in patients', these data further support the application of this antigen as an immuno-therapeutical target for myelogenous leukaemias.
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