T-CELL RECEPTOR V-BETA GENE-EXPRESSION IN MONOZYGOTIC TWINS - DISCORDANCE IN CD8 SUBSET AND IN DISEASE STATES

The peripheral T cell repertoire is shaped by positive and negative se lection. These intrathymic events are dependent on the direct interact ion of MHC and TCR molecules. Inasmuch as one possible mechanism for H LA-linked disease involves the role that these molecules play in shapi ng the peripheral T cell repertoire, an understanding of how stable th e repertoire remains is an important question that will influence futu re studies. The purpose of this study was to analyze the stability of the T cell repertoire in monozygotic twins. To investigate this questi on the percentage of CD4 and CD8 T cells expressing TCR Vbeta gene pro ducts was determined for seven sets of healthy monozygotic twins ages 2 through 44. Vbeta expression was determined by three-color flow cyto metric analysis using antibodies to Vbeta-5.1, -5.2, -5.3, -6.7, -8, a nd -12. The percentage of CD4 cells expressing each Vbeta gene was hig hly concordant between twins. In contrast, differences were noted for Vbeta expression within the CD8 subset. This was especially marked whe n sets of twins were studied (n = 3) where one individual had an under lying disease. Although expression in the CD4 subset was again concord ant, significant differences were noted within the CD8 subset compared to the healthy twin. These data indicate that in both health and dise ase, the CD4 T cell repertoire is tightly regulated although often siz able differences have developed in the CD8 compartment.