The alpha beta T-cell receptor repertoire in inclusion body myositis: diverse patterns of gene expression by muscle-infiltrating lymphocytes

J Autoimmun. 1994 Jun;7(3):321-33. doi: 10.1006/jaut.1994.1023.

Abstract

Inclusion body myositis (IBM) is one member of a group of disorders known as idiopathic inflammatory myopathies (IIM) in which autoreactive T cells directed against muscle are thought to play a primary role in disease pathogenesis. We have utilized the polymerase chain reaction to determine the pattern of alpha beta T-cell receptor (TCR) variable (V) gene expression in muscle biopsies from 13 IBM patients. In the majority of biopsies, we detected oligoclonal patterns of TCR V gene expression by muscle-infiltrating lymphocytes; an average of six out of the 22 TCR V alpha gene families surveyed and seven out of 24 TCR V beta gene families surveyed were detected per biopsy. While no TCR V alpha gene families were over-represented in our survey, TCR V beta 3 and V beta 6 gene usage was a prominent feature of IBM muscle biopsies. TCR gene expression was characterized further by analysing the junctional sequence composition of both V beta 3 and V beta 6 clones from muscle biopsies of the IBM patients. A large number of structurally diverse V beta 3 and V beta 6 clonotypes were identified from these patients demonstrating a polyclonal pattern of T cell infiltration. These data, while describing prominent TCR V beta 3 and V beta 6 gene detection, do not suggest that a common antigen-driven T-cell response promotes chronic inflammation in muscle of IBM patients.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Base Sequence
  • DNA Primers
  • Female
  • Gene Expression
  • Humans
  • Inclusion Bodies*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Myositis / immunology
  • Myositis / metabolism*
  • Myositis / pathology
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • DNA Primers
  • Peptides
  • Receptors, Antigen, T-Cell, alpha-beta