人类基因组包含数十万个古代逆转录病毒的整合，这些整合是在数百万年的进化过程中积累的。为了减少基因组的进一步扩增，宿主通过表观遗传抑制来阻止这些内源性逆转录病毒 (ERV) 的转录，并且随着进化时间的推移，ERV 会因突变和缺失的积累而丧失能力。然而，最近内源化的 ERV 群体的几个成员仍然保留产生病毒 RNA、逆转录病毒蛋白和更高阶结构（包括病毒粒子）的能力。病毒特征的保留，加上表观遗传抑制的可逆性，特别是在癌症中，允许免疫学上意想不到的ERV表达，适应性免疫系统将其视为真正的逆转录病毒感染，并对其做出反应。因此，已在多种疾病中以及偶尔在健康个体中检测到与 ERV 抗原反应的抗体。尽管它们是自身的一部分，但 ERV 抗原的逆转录病毒遗留物以及与疾病状态的关联以及可能的疾病状态的因果关系可能将它们与典型的自身抗原区分开来。因此，针对 ERV 抗原的抗体的致病能力或实际上的宿主保护能力可能取决于具体情况。在这里，我们回顾了典型 ERV 蛋白的免疫原性，重点是抗体反应及其潜在的疾病影响。© 2024 作者。约翰·威利出版的免疫学评论

The human genome harbors hundreds of thousands of integrations of ancient retroviruses, amassed over millions of years of evolution. To reduce further amplification in the genome, the host prevents transcription of these now endogenous retroviruses (ERVs) through epigenetic repression and, with evolutionary time, ERVs are incapacitated by accumulating mutations and deletions. However, several members of recently endogenized ERV groups still retain the capacity to produce viral RNA, retroviral proteins, and higher order structures, including virions. The retention of viral characteristics, combined with the reversible nature of epigenetic repression, particularly as seen in cancer, allow for immunologically unanticipated ERV expression, perceived by the adaptive immune system as a genuine retroviral infection, to which it has to respond. Accordingly, antibodies reactive with ERV antigens have been detected in diverse disorders and, occasionally, in healthy individuals. Although they are part of self, the retroviral legacy of ERV antigens, and association with and, possibly, causation of disease states may set them apart from typical self-antigens. Consequently, the pathogenic or, indeed, host-protective capacity of antibodies targeting ERV antigens is likely to be context-dependent. Here, we review the immunogenicity of typical ERV proteins, with emphasis on the antibody response and its potential disease implications.© 2024 The Author(s). Immunological Reviews published by John Wiley & Sons Ltd.