Spontaneous development of protective anti-T cell receptor autoimmunity targeted against a natural EAE-regulatory idiotope located within the 39-59 region of the TCR-Vβ8.2 chain

G. A. Hashim, H. Offner, Ying Wang Run Ying Wang, K. Shukla, E. Carvalho, W. J. Morrison, A. A. Vandenbark

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16 Scopus citations

Abstract

The development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats is mediated by Vβ8.2+ T cells specific for myelin basic protein. One consequence of this biased expression of Vβ8.2 is the spontaneous development of regulatory T cells and antibodies against residues 39-59 of the Vβ8.2 sequence. Moreover, a synthetic Vβ8.2-39-59 peptide could induce protection against and speed recovery from EAE. T cells and antibodies specific for Vβ8.2-39-59 could transfer protection from EAE. Recently, we reported that the protective T cell epitope is subsumed within the Vβ8-44-54 sequence. We now report that protection induced by Vβ8-44-54 lasted at least 102 days and produced 'split tolerance,' enhancing anti-myelin basic protein antibody titers but reducing anti-myelin basic protein T cell frequency. The shorter Vβ8-44-54 peptide induced a distinct set of antibodies that did not cross-react with the longer Vβ8.2-39-59 peptide, although both specificities could stain Vβ8.2+ T cells and were equally protective against EAE. However, the Vβ8.2-39-59 peptide, but not the Vβ8-44-54 peptide, would appear to represent the natural idiotope: antibodies to Vβ8.2-39-59 that develop spontaneously during EAE could be boosted to higher titers only by the Vβ8.2-39-59, but not by other TCR peptides from the Vβ8.2 sequence, including Vβ8-44-54 that contains the functional T cell epitope. These results suggest that natural processing of the TCR Vβ-chain favors the formation of a peptide that resembles the Vβ8.2-39-59 sequence. The B cell epitope present on the Vβ8-44-54 sequence was evident only in the absence of residues 39-43 and 55-59, suggesting that the two peptides possess distinct conformations. However, the Vβ8-44-54 B cell epitope is most likely expressed on the Vβ8.2+ T cells, either as a low affinity determinant on the intact TCR α/β heterodimer or as a cryptic epitope bound in the cleft of surface MHC molecules.

Original languageEnglish (US)
Pages (from-to)2803-2809
Number of pages7
JournalJournal of Immunology
Volume149
Issue number8
StatePublished - Jan 1 1992

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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