Epitope specificity and V gene expression of cerebrospinal fluid T cells specific for intact versus cryptic epitopes of myelin basic protein

Karuturi Satyanarayana, Yuan K. Chou, Dennis Bourdette, Ruth Whitham, George A. Hashim, Halina Offner, Arthur A. Vandenbark

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Recent evidence supports the possible involvement of myelin basic protein (BP) as one of the target autoantigens in multiple sclerosis (MS), including elevated frequencies of MS blood and cerebrospinal fluid (CSF) T cells, and the presence in MS plaque tissue of Vβ gene sequences and CDR3 motifs characteristic of BP-reactive T cells. Because of its proximity to the target organ, the CSF has long been thought to harbor T cells involved in the pathogenic process. In order to evaluate their frequency and response characteristics, BP-reactive T cells were isolated by limiting dilution from the CSF of patients with MS and other neurological diseases (OND) for quantitation and determination of epitope specificity and Vα and Vβ gene expression. In addition to isolates responsive to intact BP epitopes that were present at a significantly higher frequency in MS versus OND CSF, we here describe a second clonotype responsive to 'cryptic' BP epitopes that is present at approximately equal frequencies in MS and OND patients. In spite of their difference in recognition of intact versus 'cryptic' BP determinants, both clonotypes predominantly recognized epitopes in the N terminal half of human BP, using a similar V gene repertoire that included biased use of Vα2 and to a lesser degree Vβ7 and Vβ18. These V gene biases were not related to the epitope specificity of the T cells, indicating that V gene selection is not epitope-driven. These data suggest that there is differential recognition of intact versus 'cryptic' BP determinants in MS versus OND patients that may be related to the processing and presentation of BP to the immune system.

Original languageEnglish (US)
Pages (from-to)57-67
Number of pages11
JournalJournal of Neuroimmunology
Volume44
Issue number1
DOIs
StatePublished - Apr 1993

Keywords

  • Cerebrospinal fluid T cells
  • Multiple sclerosis
  • T cell receptor usage

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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