Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Netherlands Proteomics Centre, Utrecht, Netherlands.
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Netherlands Proteomics Centre, Utrecht, Netherlands.
Mol Cell Proteomics. 2021;20:100089. doi: 10.1016/j.mcpro.2021.100089. Epub 2021 Apr 29.
Human leukocyte antigen (HLA) molecules play critical roles in our adaptive immune system by signaling a cell's health status to the immune system, through presentation of small peptides. Understanding HLA biology is important because of its prominent role in autoimmune diseases and cancer immunotherapy. Although both the HLA class I and class II antigen processing and presentation pathways have been studied extensively, the fundamental rules in HLA class II antigen presentation still remain less understood. To clarify the mechanistic and adaptive differences between the HLA systems, we challenged a B lymphoblastic cell line (JY), widely used as model system in studying antigen presentation, with a high temperature treatment to mimic a "fever-like state", representing one of the most common physiological responses to infection. In the absence of real invading pathogenic peptides to present, we could focus on delineating the intrinsic HLA pathway adaptations in response to high temperature in this particular cell line. Following a three-pronged approach, we performed quantitative analyses of the proteome, the HLA class I ligandome, as well as the HLA class II ligandome. The data reveals that elevated temperature may already prepare these cells for an immune-like response through increased HLA class II presentation capacity and specific release of, from the invariant chain originating, CLIP peptides. Interestingly, at high temperature, prominent changes in the composition of the CLIP repertoire were observed, with enrichment of peptides containing C-terminal extensions beyond the CLIP-core region. Collectively, these illustrate intriguing temperature sensitive adaptations in this B cell line.
人类白细胞抗原（HLA）分子通过呈递小肽向免疫系统提示细胞的健康状态，在我们的适应性免疫系统中发挥着关键作用。了解 HLA 生物学很重要，因为它在自身免疫性疾病和癌症免疫治疗中起着重要作用。尽管 HLA Ⅰ类和Ⅱ类抗原加工和呈递途径都得到了广泛研究，但 HLA Ⅱ类抗原呈递的基本规则仍知之甚少。为了阐明 HLA 系统之间的机制和适应性差异，我们用高温处理来模拟“发热样状态”，挑战了一种 B 淋巴母细胞系（JY），该细胞系广泛用作研究抗原呈递的模型系统。这种处理方式代表了最常见的感染生理反应之一。在不存在真正入侵的致病肽来呈递的情况下，我们可以专注于描绘该特定细胞系中针对高温的固有 HLA 途径适应性。通过三管齐下的方法，我们对蛋白质组、HLA Ⅰ类配体组以及 HLA Ⅱ类配体组进行了定量分析。数据表明，升高的温度可能通过增加 HLA Ⅱ类呈递能力和从不变链起源的 CLIP 肽的特定释放，使这些细胞为免疫样反应做好准备。有趣的是，在高温下，观察到 CLIP 库的组成发生了显著变化，富含含有 CLIP 核心区域以外的 C 末端延伸的肽。总的来说，这些结果说明了该 B 细胞系中存在有趣的温度敏感适应性。
