BIASED T-CELL RECEPTOR V-BETA GENE USAGE DURING SPECIFIC STAGES OF THE DEVELOPMENT OF AUTOIMMUNE SIALADENITIS IN THE MRL/LPR MOUSE MODEL OF SJOGRENS-SYNDROME

Objective. To analyze the repertoire of T cell receptor (TCR) V-beta genes transcribed and expressed within the autoimmune lesions of the salivary gland in the MRL/lpr mouse model of Sjogren's syndrome, Methods. 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. Results, 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. Conclusion, Our data suggest that in the MRL/Ipr mouse model of Sjogren'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.