Autoimmune susceptible HLA class II motifs facilitate the presentation of modified neoepitopes to potentially autoreactive T cells

IF 3.7 4区 医学 Q2 CELL BIOLOGY Cellular immunology Pub Date : 2023-08-01 DOI:10.1016/j.cellimm.2023.104729
Antonis K. Moustakas , Hai Nguyen , Eddie A. James , George K. Papadopoulos
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引用次数: 1

Abstract

Rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D), and celiac disease (CD), are strongly associated with susceptible HLA class II haplotypes. The peptide-binding pockets of these molecules are polymorphic, thus each HLA class II protein presents a distinct set of peptides to CD4+ T cells. Peptide diversity is increased through post-translational modifications, generating non-templated sequences that enhance HLA binding and/or T cell recognition. The high-risk HLA-DR alleles that confer susceptibility to RA are notable for their ability to accommodate citrulline, promoting responses to citrullinated self-antigens. Likewise, HLA-DQ alleles associated with T1D and CD favor the binding of deamidated peptides. In this review, we discuss structural features that promote modified self-epitope presentation, provide evidence supporting the relevance of T cell recognition of such antigens in disease processes, and make a case that interrupting the pathways that generate such epitopes and reprogramming neoepitope-specific T cells are key strategies for effective therapeutic intervention.

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自身免疫易感的HLA II类基序促进修饰的新表位向潜在的自身反应性T细胞呈递
类风湿性关节炎(RA)、多发性硬化症(MS)、1型糖尿病(T1D)和乳糜泻(CD)与易感HLA II类单倍型密切相关。这些分子的肽结合口袋是多态的,因此每个HLA II类蛋白向CD4+T细胞呈现一组不同的肽。肽多样性通过翻译后修饰增加,产生增强HLA结合和/或T细胞识别的非模板化序列。赋予RA易感性的高危HLA-DR等位基因因其适应瓜氨酸的能力而引人注目,从而促进对瓜氨酸化自身抗原的反应。同样,与T1D和CD相关的HLA-DQ等位基因有利于脱酰胺肽的结合。在这篇综述中,我们讨论了促进修饰的自身表位呈递的结构特征,提供了支持T细胞识别此类抗原在疾病过程中的相关性的证据,并证明阻断产生此类表位的途径和重新编程新表位特异性T细胞是有效治疗干预的关键策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
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