Biased T cell receptor V beta gene usage during specific stages of the development of autoimmune sialadenitis in the MRL/lpr mouse model of Sjögren's syndrome.

Abstract

To analyze the repertoire of T cell receptor (TCR) V beta gene transcribed and expressed within the autoimmune lesions of the salivary gland in the MRL/lpr mouse model of Sjögren's syndrome. Monoclonal antibodies (MAb) were used to determine the prevalence of selected V gene elements on T cell infiltrates from salivary glands of MRL/lpr mice. To analyze TCR V beta gene usage, we used reverse-transcriptase polymerase chain reaction (RT-PCR) and single-strand conformational polymorphism (SSCP) analyses. A predominance of V beta 8+ T cells was detected within the inflammatory lesions during development of autoimmune disease (confirmed by flow cytometry). RT-PCR analysis revealed that in autoimmune sialadenitis, the predominant expression of the V beta 8 gene segment began in the early stages of disease (2-month-old mice) and increased over time. Extensive age-related diversity of TCR V beta gene usage was also observed. SSCP analysis demonstrated a distinct and common binding pattern of the V beta 8 gene PCR product from the cell infiltrates during the course of the disease. Our data suggest that in the MRL/lpr mouse model of Sjögren's syndrome, there is restricted usage of TCR V beta elements according to the stage of the disease, and that V beta 8 are probably used preferentially in the recognition of a single unknown self antigen in the salivary gland.