Ras-Carmona Alvaro, Lehmann Alexander, Reche Pedro A
Department of Immunology, Ophthalmology and ENT, Faculty of Medicine, University Complutense of Madrid, Pza Ramon y Cajal S/N, 28040 Madrid, Spain.
Int J Mol Sci. 2025 Jun 24;26(13):6041. doi: 10.3390/ijms26136041.
Self/non-self-discrimination is a fundamental aspect of adaptive immunity, which helps prevent harmful autoimmune responses. However, infectious agents can also act as environmental catalysts for autoimmune diseases. In this study, we investigated the role of molecular mimicry to self-antigens in epitope recognition in relation to infectious and autoimmune diseases. To this end, we performed BLAST searches against the human proteome, utilizing known virus-specific B and T cell peptide epitopes identified in association with autoimmune or infectious diseases in humans as our queries. Additionally, similar control analyses were carried out using non-B and non-T cell epitopes, consisting of random viral peptide sequences. Overall, our results endorsed a major role of molecular mimicry in instigating or sustaining autoimmunity associated with viral infections and challenged the prevailing view on self/non-self-discrimination for T cells. Additionally, we uncovered many virus-specific epitopes among those identified in association with infectious diseases with high similarity to self-antigens, which are primarily derived from human coronaviruses and various flaviviruses. Recognition of these epitopes could lead to autoimmunity against human proteins that are in cellular components concerning cell motility, cell membrane projections, and cellular synapses.
自我/非自我识别是适应性免疫的一个基本方面，有助于预防有害的自身免疫反应。然而，感染因子也可作为自身免疫性疾病的环境催化剂。在本研究中，我们调查了分子模拟自身抗原在与感染性疾病和自身免疫性疾病相关的表位识别中的作用。为此，我们利用与人类自身免疫性或感染性疾病相关的已知病毒特异性B和T细胞肽表位作为查询序列，对人类蛋白质组进行了BLAST搜索。此外，使用由随机病毒肽序列组成的非B和非T细胞表位进行了类似的对照分析。总体而言，我们的结果证实了分子模拟在引发或维持与病毒感染相关的自身免疫中起主要作用，并对T细胞自我/非自我识别的主流观点提出了挑战。此外，我们在与感染性疾病相关的表位中发现了许多与自身抗原有高度相似性的病毒特异性表位，这些表位主要来源于人类冠状病毒和各种黄病毒。对这些表位的识别可能导致针对与细胞运动、细胞膜突起和细胞突触有关的细胞成分中的人类蛋白质的自身免疫。
