PREDOMINANT T-CELL RECEPTOR V-BETA USAGE OF INTRAEPITHELIAL LYMPHOCYTES DURING THE IMMUNE-RESPONSE TO ENTERIC REOVIRUS INFECTION

Previous studies have found that intraepithelial lymphocytes (IEL) con tain virus-specific cytotoxic T lymphocytes (CTL) that increase dramat ically during the course of virus infection, In the present study, the T-cell receptor (TCR) V beta pattern used by IEL against reovirus ent eric infection was investigated both in conventional and in germfree m ice, IEL were isolated by a modified rapid method, and their expressio n of 13 TCR V beta s was examined by flow cytometric analysis, The vir us-specific CTL activity of each TCR V beta subset was assessed by sub traction with coated Dyna beads by a nonradioactive assay, There was a preferential perturbation of TCR V beta s following virus challenge, including increases in cells expressing V beta 7, -12, -14, and -17 in conventional mice and V beta 2, -12, and -17 in germfree mice, In con ventionally reared mice, IEL maintained and restimulated in culture ha d a preferential use of TCR V beta 9, -12, and -17, TCR V beta 12 and -17 subfamilies were found amplified in all conditions, Furthermore, T CR V beta 12 and -17 accounted for 37 and 77% of the virus-specific CT L activity, respectively, after in vitro restimulation. This study pro vides evidence that virus-specific CTL activity may be due to the olig oclonal expansion of TCR V beta subfamilies in IEL, Our findings sugge st that in vivo infection selectively presents few T-cell epitopes and that the correct identification of these T-cell epitopes would increa se the likelihood of success when designing subunit vaccines.