Print Email Facebook Twitter Mistaken self, a novel model that links microbial infections with myelin-directed autoimmunity in multiple sclerosis Title Mistaken self, a novel model that links microbial infections with myelin-directed autoimmunity in multiple sclerosis Author van Noort, J.M. Bajramovic, J.J. Plomp, A.C. van Stipdonk, M.J.B. Publication year 2000 Abstract Several findings indicate that infectious events play a role in the pathogenesis of multiple sclerosis (MS). At the same time, T-cell autoimmunity to myelin antigens is widely believed to be crucial to the development of MS lesions. Several mechanisms have been put forward to explain the presumed link between microbial infections and myelin-directed autoimmunity. These include molecular mimicry, bystander activation including epitope spreading and superantigenic activation of T cells. Evidence that either one of these mechanisms actually occurs in MS patients, however, is still weak. Also, none of the above mechanisms explain why MS is unique to humans. We propose an alternative link between microbial infection and myelin autoimmunity, which we refer to as 'mistaken self'. In this mechanism, peripheral microbial infections of lymphoid cells prime the human T-cell repertoire not only to microbial antigens but also to the stress protein alpha B-crystallin that is expressed de novo in infected lymphoid cells. Subsequently, stress-induced accumulation of this self antigen in oligodendocytes/myelin can provoke pro-inflammatory responses as the recruited memory T-cell repertoire then mistakes the self protein for a microbial antigen. In this paper we review the currently available evidence that 'mistaken self' centering on alpha B-crystallin represents a powerful source of anti-myelin autoimmunity in a way that is unique to humans. Copyright (C) 2000 Elsevier Science B.V. Chemicals/CAS: CrystallinsChemicals/CAS: Crystallins Subject Alpha B-crystallinAutoimmunityMicrobial infectionMultiple sclerosisT cellsAutoantigenCrystallinMyelinAnimal experimentAnimal modelAutoimmunityBacterial infectionMouseNonhumanRatReviewStressT lymphocyteAutoimmunityBacterial InfectionsCrystallinsHumansImmunologic MemoryMultiple SclerosisMyelin SheathOrgan SpecificityT-Lymphocytes To reference this document use: http://resolver.tudelft.nl/uuid:e9eacb21-dc40-41d3-bd63-95323d08492b DOI https://doi.org/10.1016/s0165-5728(00)00181-8 TNO identifier 235577 ISSN 0165-5728 Source Journal of Neuroimmunology, 105 (1), 46-57 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.