Predominant TCR-αβ variable and joining gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies

Terrance P. O'Hanlon, Marines C. Dalakas, Paul H. Plotz, Frederick W. Miller

Research output: Contribution to journalArticle

Abstract

The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases in which autoreactive T cells are thought to play a pathogenetic role. We have determined the pattern of TCR-αβ gene expression by muscle-infiltrating lymphocytes within clinically and serologically defined groups of IIM patients. We utilized the PCR to study TCR V gene expression in muscle biopsies from nine polymyositis (PM) and eight dermatomyositis (DM) patients, all of whom had autoantibodies directed against histidyl-transfer RNA synthetase (anti-Jo-1 autoantibodies). While the TCR repertoire in DM patients was generally polyclonal, an oligoclonal profile characterized PM patients. Certain V gene families were predominantly expressed; Vα1 and Vβ6 gene families were detected in 82 and 91% of PM biopsies, respectively. TCR expression was characterized further by analyzing J gene usage from four PM patients expressing the Vβ6 gene. Sequence analysis of 40 independent recombinants (10 per patient) identified only seven Vβ6 clonotypes and restricted usage of the related Jβ2.1, -2.3, and -2.7 genes. These data, describing predominant TCR V and J gene usage by muscle-infiltrating lymphocytes in myositis patients, suggest that Ag-driven T cell responses may play a primary role in mediating some forms of the IIM.

Original languageEnglish (US)
Pages (from-to)2569-2576
Number of pages8
JournalJournal of Immunology
Volume152
Issue number5
StatePublished - Mar 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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