Analysis of the Peripheral T-Cell Receptor VP Repertoire in Newly Diagnosed Patients with Type I Diabetes

Abstract

Type I diabetes is an autoimmune disease characterised by a marked activation of peripheral T cells around the time of clinical diagnosis. Studies of T-cell antigen receptor Vp (TCRBV) gene usage in type I diabetes have been conflicting. Usng a semi-quantitative polymerase chain reaction technique and flow cytometry we have investigated the TCRBV gene usage of 13 newly diagnosed patients with type I diabetes and 11 normal healthy controls. No preferential TCRBV gene usage was found between patients and controls even after matching for HLA-DR3 and/or -DR4. In addition, no significant differences in TCRBV gene usage were found between sequential samples taken over a period of up to 7 months following diagnosis. These results suggest that the TCR repertoire of these patients is heterogeneous and it is unlikely that a single ‘pathogenic’ T-cell clone is dominant at the clinical onset of the disease.

Key Words:

• T-cell receptor Vp gene repertoire
• polymerase chain reaction
• flow cytometry
• type I diabetes
• autoimmune disease
• T-cell tolerance