Homologies between T cell receptor junctional sequences unique to multiple sclerosis and T cells mediating experimental allergic encephalomyelitis

Mark Allegretta, Richard J. Albertini, Mark D. Howell, Lawrence R. Smith, Roland Martin, Henry F. McFarland, Subramamiam Sriram, Steven Brostoff, Lawrence Steinman

Research output: Contribution to journalArticlepeer-review

Abstract

The selection of T cell clones with mutations in the hypoxanthine guanine phosphoribosyltransferase (hprt) gene has been used to isolate T cells reactive to myelin basic protein (MBP) in patients with multiple sclerosis (MS). These T cell clones are activated in vivo, and are not found in healthy individuals. The third complementarity determining regions (CDR3) of the T cell receptor (TCR) α and β chains are the putative contact sites for peptide fragments of MBP bound in the groove of the HLA molecule. The TCR V gene usage and CDR3s of these MBP-reactive hprt- T cell clones are homologous to TCRs from other T cells relevant to MS, including T cells causing experimental allergic encephalomyelitis (EAE) and T cells found in brain lesions and in the cerebrospinal fluid (CSF) of MS patients. In vivo activated MBP-reactive T cells in MS patients may be critical in the pathogenesis of MS.

Original languageEnglish (US)
Pages (from-to)105-109
Number of pages5
JournalJournal of Clinical Investigation
Volume94
Issue number1
StatePublished - Jul 1994
Externally publishedYes

Keywords

  • hypoxanthine phosphoribosyltransferase
  • in vivo
  • mutation
  • myelin basic protein
  • T lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

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