Background During infection with the Lyme arthritis (LA) pathogen Borrelia burgdorferi, T-cell responses to both host and pathogen are dysregulated, resulting in chronic infection and frequent development of autoimmunity. Methods To assess CD4+ T-cell epitopes presented during development of LA, we used an unbiased, immunopeptidomics approach to characterize the major histocompatibility complex (MHC) class II immunopeptidome in B burgdorferi-infected C57BL/6 (B6) mice, which develop mild, self-limiting LA, and infected B6 Il10−/− mice, which develop severe, persistent LA at 0, 4, and 16 weeks postinfection (22–23 mice per group). Results Peptides derived from proteins involved in adaptive T- and B-cell responses and cholesterol metabolism, including human Lyme autoantigen apolipoprotein B-100 (apoB-100), were enriched in infected Il10−/− mice; whereas peptides derived from proteins involved in neutrophil extracellular net formation were enriched in infected B6 mice. Presentation of apoB-100 peptides showed evidence of epitope expansion during infection. Of several identified B burgdorferi peptides, only 1, a methyl-accepting chemotaxis protein peptide Mcp4442–462, was immunogenic. Conclusions ApoB-100, a human Lyme autoantigen, undergoes marked epitope expansion during LA development. The paucity of immunogenic B burgdorferi epitopes supports previous findings suggesting CD4+ T-cell responses are suppressed in murine LA.

中文翻译：

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小鼠莱姆关节炎中莱姆自身抗原载脂蛋白 B-100 和伯氏疏螺旋体 Mcp4 的主要组织相容性复合体 II 类表位鉴定


背景 在感染莱姆关节炎 （LA） 病原体伯氏疏螺旋体期间，T 细胞对宿主和病原体的反应失调，导致慢性感染和自身免疫的频繁发展。方法 为了评估 LA 发育过程中呈现的 CD4 + T 细胞表位，我们使用无偏倚的免疫消化组学方法来表征伯氏疏螺旋体感染的 C57BL/6 （B6） 小鼠的主要组织相容性复合体 （MHC） II 类免疫肽组，这些小鼠发展为轻度、自限性 LA，以及感染的 B6 Il10-/- 小鼠，在感染后 0、4 和 16 周发展为严重、持续的 LA（每组 22-23 只小鼠）。结果 源自参与适应性 T 细胞和 B 细胞反应和胆固醇代谢的蛋白质的肽，包括人莱姆自身抗原载脂蛋白 B-100 （apoB-100），在感染的 Il10−/− 小鼠中富集;而来自参与中性粒细胞胞外网形成的蛋白质的肽在感染的 B6 小鼠中富集。apoB-100 肽的呈递显示感染期间表位扩增的证据。在几种已鉴定的伯氏疏螺旋体肽中，只有 1 种，一种甲基接受趋化蛋白肽 Mcp4442-462，具有免疫原性。结论 ApoB-100 是一种人莱姆自身抗原，在 LA 发育过程中经历了明显的表位扩增。免疫原性伯氏疏螺旋体表位的缺乏支持先前的发现，即小鼠 LA 中 CD4 + T 细胞反应受到抑制。