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

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-alpha beta 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; V alpha 1 and V beta 6 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 V beta 6 gene. Sequence analysis of 40 independent recombinants (10 per patient) identified only seven V beta 6 clonotypes and restricted usage of the related J beta 2.1, -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.

• Authors: T P O'Hanlon, M C Dalakas, P H Plotz, F W Miller
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 152 Issue 5 Pg. 2569-76 (Mar 01 1994) ISSN: 0022-1767 [Print] United States
• PMID: 8133064 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• Adult
• Aged
• Amino Acid Sequence
• Autoantibodies
• Base Sequence
• DNA Primers (genetics)
• Female
• Gene Expression
• Humans
• Male
• Middle Aged
• Molecular Sequence Data
• Muscles (immunology)
• Myositis (genetics, immunology)
• Receptors, Antigen, T-Cell, alpha-beta (genetics)
• T-Lymphocytes (immunology)