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1、ChapterC7CORONAVIRUSESANDNEUROANTIGENS:myelinproteins,myelingenesPierreJ.Talbot,AnnieBoucher,PierreDuquette1,andEdithGruslinlNRS-lnstitutArmand-Frappier,Institutnationaldelarecherchescientifique,UniversitdduQuebec,Laval,Quebec,CanadaH7V1B,and~PavilionNotre-Dame,Centrehospit
2、alierdel'Universit~deMontreal,Universit~deMontreal,Montreal,Quebec,CanadaH2L4K8Abstract:Multiplesclerosis(MS)isanautoimmunediseaseinwhichautoreactiveTcellsspecifictocentralnervoussystem(CNS)myelinantigensareactivated.Althoughdiseaseetiologyremainsunknown,coronavirusesaresus
3、pectedtobeinvolvedinMSpathology.Molecularmimicry,therecognitionoftwoantigensbyasingleimmunecell,couldbethemechanismexplainingthelinkbetweenaviralinfectionandMSthroughactivationofmyelin-reactiveTcellsbyavirusinfectioninageneticallypredisposedindividual.Evidencesupportingthis
4、hypothesisinhumanshasbeenaccumulatedinourlaboratory.Humancoronavirus(HCoV)-myelincross-reactiveT-celllines(TCL)werepredominantlyfoundinMSpatientscomparedtopatientswithotherneurologicalorinflammatorydiseases,orhealthycontrols.Moreover,virus-myelinTcellcross-reactivitywasconf
5、irmedattheclonallevel.Molecularmimicrybetweeninfectiouspathogenssuchastheubiquitoushumanrespiratorycoronavirusescould,ingeneticallysusceptibleindividuals,playaroleleadingtothedevelopmentofMS.Togetherwithotherpossiblemechanismssuchasbystandereffects,epitopespreadingorevensup
6、erantigenicactivities,thispathogen-associatedimmuneinductioncouldplayaroleinmaintainingandbroadeningtheautoimmuneresponseassociatedwithMSpathology.Keywords:autoimmunity,Tcells,centralnervoussystem,virus,molecularmimicry1.INTRODUCTIONMultiplesclerosis(MS)isanautoimmunediseas
7、eofthecentralnervoussystem(CNS)characterizedbyinflammationandmyelindestruction.Even782ChapterC7thoughMSwasdescribedmorethan130yearsago,itsexactetiologyremainsunknown.AgeneticpredispositionissuggestedandHLAgenesaresuspectedtobeinvolved(1,2).Environmentalfactorsarealsoassocia
8、tedwiththetriggeringofthispathology.Indeed,epidemiologicalstudieswithidenticaltwin