Secreted HLA-Fc fusion profiles immunopeptidome in hypoxic PDAC and cellular senescence.
Secreted HLA-Fc fusion profiles immunopeptidome in hypoxic PDAC and cellular senescence.
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DOI：
10.1093/pnasnexus/pgad400
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发表时间：
2023-12
期刊：
影响因子：
--
通讯作者：
Wells, James A.
中科院分区：
文献类型：
--
作者：
Rettko, Nicholas J.;Kirkemo, Lisa L.;Wells, James A.
人类白细胞抗原（HLA）主要从细胞表面的细胞内蛋白质呈递肽。由于这些复合物可以作为疾病中的生物标志物，因此正确鉴定源自疾病相关抗原的肽和相应的呈递HLA对于设计和执行治疗策略是重要的。然而，目前用于免疫肽组分析的质谱法需要大量且复杂的样品输入，阻碍了某些疾病表型的研究，并降低了肽和等位基因鉴定的置信度。在这里，我们描述了一个分泌的HLA（sHLA）-Fc融合构建简单的单一HLA等位基因分析缺氧胰腺导管腺癌（PDAC）和细胞衰老。该方法简化了样品制备，实现了时间控制，并提供了等位基因限制的靶标鉴定。在2种不同的HLA等位基因和7种细胞系中鉴定了超过30，000种独特的HLA相关肽，其中新发现了109，300种肽。sHLA-Fc融合捕获技术具有加快免疫肽组学和促进HLA-肽复合物的治疗兴趣的潜力。
Human leukocyte antigens (HLA) present peptides largely from intracellular proteins on cell surfaces. As these complexes can serve as biomarkers in disease, proper identification of peptides derived from disease-associated antigens and the corresponding presenting HLA is important for the design and execution of therapeutic strategies. Yet, current mass spectrometry methods for immunopeptidomic profiling require large and complex sample inputs, hindering the study of certain disease phenotypes and lowering confidence in peptide and allele identification. Here, we describe a secreted HLA (sHLA)-Fc fusion construct for simple single HLA allele profiling in hypoxic pancreatic ductal adenocarcinoma (PDAC) and cellular senescence. This method streamlines sample preparation, enables temporal control, and provides allele-restricted target identification. Over 30,000 unique HLA-associated peptides were identified across 2 different HLA alleles and 7 cell lines, with ∼9,300 peptides newly discovered. The sHLA-Fc fusion capture technology holds the potential to expedite immunopeptidomics and advance therapeutic interest in HLA-peptide complexes.
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影响因子：
2.8
作者：
Fields, Aaron J.;Berg-Johansen, Britta;Metz, Lionel N.;Miller, Stephanie;La, Brandan;Liebenberg, Ellen C.;Coughlin, Dezba G.;Graham, James L.;Stanhope, Kimber L.;Havel, Peter J.;Lotz, Jeffrey C.
通讯作者：
Lotz, Jeffrey C.
饮食中晚期糖基化终产物的消耗导致小鼠椎间盘机械硬化。
影响因子：
4.3
作者：
Krishnamoorthy D;Hoy RC;Natelson DM;Torre OM;Laudier DM;Iatridis JC;Illien-Jünger S
通讯作者：
Illien-Jünger S
影响因子：
2.8
作者：
Shadwick, Robert E.
通讯作者：
Shadwick, Robert E.
DOI：
10.3102/1076998610396889
发表时间：
2011-12
期刊：
Journal of educational and behavioral statistics : a quarterly publication sponsored by the American Educational Research Association and the American Statistical Association
影响因子：
--
作者：
Lazar AA;Zerbe GO
通讯作者：
Zerbe GO
影响因子：
3
作者：
MARCHAND, F;AHMED, AM
通讯作者：
AHMED, AM