Class II-restricted bifunctional T-cell hybridomas reactive to self- and foreign myelin basic protein.
To study the cross-reactivity and functional properties oF murine T cells specific for myelin basic protein (MBP), a panel of 15 interleukin-2(IL-2)-releasing T-cell hybridomas was produced from SJL/J mice immunized either with human MBP or alternatively with a peptide corresponding to the known encephalitogenic sequence for SJL/J mice at positions 89-106. Hybridomas were I-As-restricted and activated by an MBP challenge as low as 20 nM. Cross-reactivity to other MBP indicated at least three immunodominant specificities for xenogeneic determinants, which could be further subdivided on the basis of antigen-independent reactivity to allogeneic stimulator cells. In addition, two self-specificities were demonstrated, one of which was to a determinant outside the 89-106 region. Irrespective of specificity pattern (self or foreign), all hybridomas effected antigen-dependent cytotoxicity of an antigen-presenting B-cell hybridoma (LS-102.9), which was mediated by cell contact or at close range. These findings suggest an approach to identifying new autoantigenic epitopes on MBP, and to studying T-cell-mediated effector pathways in myelin autoimmunity.
Department of Pathology, University of Manitoba Faculty of Medicine, Winnipeg, Canada.
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Rayner
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Petrycky
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D006825:Hybridomas / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D004676:Myelin Basic Protein