Exhaustive Proteome Mining for Functional MHC-I Ligands

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• 作者：Christian P. Koch ; Anna M. Perna ; Sabrina Weissm眉ller ; Stefanie Bauer ; Max Pillong ; Renato B. Baleeiro ; Michael Reutlinger ; Gerd Folkers ; Peter Walden ; Paul Wrede ; Jan A. Hiss ; Zoe Waibler ; Gisbert Schneider
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：September 20, 2013
• 年：2013
• 卷：8
• 期：9
• 页码：1876-1881
• 全文大小：261K
• 年卷期：v.8,no.9(September 20, 2013)
• ISSN：1554-8937

文摘

We present the development and application of a new machine-learning approach to exhaustively and reliably identify major histocompatibility complex class I (MHC-I) ligands among all 20⁸ octapeptides and in genome-derived proteomes of Mus musculus, influenza A H3N8, and vesicular stomatitis virus (VSV). Focusing on murine H-2K^b, we identified potent octapeptides exhibiting direct MHC-I binding and stabilization on the surface of TAP-deficient RMA-S cells. Computationally identified VSV-derived peptides induced CD8⁺ T-cell proliferation after VSV-infection of mice. The study demonstrates that high-level machine-learning models provide a unique access to rationally designed peptides and a promising approach toward 鈥渞everse vaccinology鈥?