MS-Based HLA-II Peptidomics Combined With Multiomics Will Aid the Development of Future Immunotherapies.
MS-Based HLA-II Peptidomics Combined With Multiomics Will Aid the Development of Future Immunotherapies.
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DOI：
10.1016/j.mcpro.2021.100116
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Abelin JG
中科院分区：
文献类型：
--
作者：
Taylor HB;Klaeger S;Clauser KR;Sarkizova S;Weingarten-Gabbay S;Graham DB;Carr SA;Abelin JG
免疫疗法已经出现，通过选择性调节患者的免疫反应来治疗疾病。尽管 T 细胞和 B 细胞在适应性免疫中的作用已得到充分研究，但选择免疫治疗策略的靶点仍然很困难。由于人类白细胞抗原 II 类 (HLA-II) 肽可激活 CD4+ T 细胞并调节 B 细胞活化、增殖和分化，因此这些肽抗原代表了一类潜在的免疫治疗靶点和生物标志物。为了更好地了解 HLA-II 抗原呈递如何参与疾病进展和治疗的分子基础，需要系统的 HLA-II 肽组学与健康和患病状态下不同细胞类型的多组学分析相结合。因此，基于 MS 的创新有助于研究疾病病理学与 HLA-II 肽向 CD4+ T 细胞的呈递之间的相互作用，这将有助于开发以患者为中心的免疫疗法。 HLA-II 等位基因具有高度多态性并具有独特的肽结合基序。 HLA-II 处理和呈递途径非常复杂且难以预测。基于 MS 的 HLA-II 肽组学能够深入了解 HLA-II 生物学。与 HLA-II 结合的肽抗原可能是免疫治疗靶点的来源。尽管利用基于 MS 的 HLA-II 肽组学仍然存在挑战，但对疾病病理学与 HLA-II 肽向 CD4+ T 细胞的呈递之间的相互作用的研究将有助于未来免疫疗法的开发。在这篇综述文章中，我们讨论了我们目前对 HLA-II 肽组学的理解和该领域的突出问题，以及基于 MS 的创新如何使我们能够填补知识空白并帮助提高我们选择 HLA-II 呈递抗原作为个性化免疫疗法靶点的能力。
Immunotherapies have emerged to treat diseases by selectively modulating a patient’s immune response. Although the roles of T and B cells in adaptive immunity have been well studied, it remains difficult to select targets for immunotherapeutic strategies. Because human leukocyte antigen class II (HLA-II) peptides activate CD4+ T cells and regulate B cell activation, proliferation, and differentiation, these peptide antigens represent a class of potential immunotherapy targets and biomarkers. To better understand the molecular basis of how HLA-II antigen presentation is involved in disease progression and treatment, systematic HLA-II peptidomics combined with multiomic analyses of diverse cell types in healthy and diseased states is required. For this reason, MS-based innovations that facilitate investigations into the interplay between disease pathologies and the presentation of HLA-II peptides to CD4+ T cells will aid in the development of patient-focused immunotherapies. HLA-II alleles are highly polymorphic and have unique peptide-binding motifs. HLA-II processing and presentation pathways are complex and challenging to predict. MS-based HLA-II peptidomics enables insights into HLA-II biology. Peptide antigens bound to HLA-II may be a source of immunotherapeutic targets. Although challenges remain in leveraging MS-based HLA-II peptidomics, investigations into the interplay between disease pathologies and the presentation of HLA-II peptides to CD4+ T cells will enable the development of future immunotherapies. In this Review article, we discuss our current understanding of HLA-II peptidomics and outstanding questions in the field and how MS-based innovations will enable us to fill knowledge gaps and help improve our ability to select HLA-II-presented antigens as targets for personalized immunotherapies.
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影响因子：
32.4
作者：
Abelin JG;Keskin DB;Sarkizova S;Hartigan CR;Zhang W;Sidney J;Stevens J;Lane W;Zhang GL;Eisenhaure TM;Clauser KR;Hacohen N;Rooney MS;Carr SA;Wu CJ
通讯作者：
Wu CJ
影响因子：
14.9
作者：
Andreatta, Massimo;Alvarez, Bruno;Nielsen, Morten
通讯作者：
Nielsen, Morten
影响因子：
64.8
作者：
Alspach, Elise;Lussier, Danielle M.;Schreiber, Robert D.
通讯作者：
Schreiber, Robert D.
影响因子：
9.2
作者：
Bettencourt, Paulo;Muller, Julius;McShane, Helen
通讯作者：
McShane, Helen
影响因子：
56.9
作者：
Burgdorf, Sven;Kautz, Andreas;Kurts, Christian
通讯作者：
Kurts, Christian