A MyelinBasicProteinPeptideIsRecognizedby CytotoxicT CellsintheContextofFourHLA DR 'hypesAssociatedwithMultipleSclerosis

Roland Martin,Mark D. Howell,Dolores Jaraquemada,Marjorie Flerlage,John Richert,Steven Brostoff,Eric O. Long,Dale E. McFarlin,Henry F. McFarland

msra（1991）

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Summary We haveexaminedpreviously thepeptidespecificity oftheT cellresponsetomyelinbasicprotein (MBP) inpatientswith multiplesclerosis (MS) andhealthycontrols, anddemonstratedthatan epitopespanningamino acids87-106 was frequentlyrecognized. Becausethisregionis encephalitogenic insome experimentalanimals,ithasbeenpostulatedthattheresponsetothe epitopemay haverelevancetoMS .Inthisstudy,thefinespecificity ofthisresponseisstudied usingfourwell-characterized, monospecificT celllinesfromthreeMS patientsandanidentical twin ofapatient.Eachofthelinesrecognizedapeptidewiththesamecoresequence,amino acids89-99,althoughtheresponseswereaffected tovariousdegreesbytruncations atthe000H- or NH2 terminalends of the 87-106 epitope.Importantly,theepitopewas recognizedin conjunctionwith fourdifferent HLA-DR molecules.Also,theT cellreceptor/3chainusage washeterogeneous, andeachlineexpressed adifferent VDJ sequence.The fourHLA DR molecules restricting theresponsetothisepitopehavebeenshown tobeoverrepresented inMS populations invariousgeographicareas,suggestingthattheresponsetothisregionoftheMBP molecule may be relevanttothepathogenesisofMS .Thesefindingsmay haveimportantimplications indesigningtherapeuticstrategies forthedisease .

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