T cell involvement in the inflammatory process of Crohn's Disease (CD) is evident by an increase in activated T cells and their cytokines in actively inflamed CD tissue. It has been suggested that CD may involve a superantigen based on the observation that a significant proportion of CD patients express elevated levels of V beta 8+ T cells in their peripheral blood compared to normal controls. In order to determine whether a superantigen might play a role in the pathogenesis of CD we have compared the TCR repertoires of four pairs of monozygotic twins discordant for CD. By using monozygotic twins, we could rule out the effects of HLA and other genes on the TCR repertoire. The TCR repertoires were analyzed by using a panel of V-segment-specific mAb and by quantitative polymerase chain reaction (qPCR) using V beta-specific oligonucleotide primers. In all cases the TCR repertoires of the affected and unaffected sibs were strikingly similar. We did not observe any TCR segment that was consistently altered in frequency or expression levels in all of the affected sibs compared to their identical twin. Furthermore, we did not see an increase in V beta 8+T cells in the peripheral blood of the CD sibs relative to their normal counterpart. These studies suggest that the presence of CD does not alter the TCR repertoire of peripheral blood in any obvious way and argue against the role of a superantigen in the etiology of pathogenesis of CD.