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  • Title: The expressed T cell receptor V gene repertoire of rheumatoid arthritis monozygotic twins: rapid analysis by anchored polymerase chain reaction and enzyme-linked immunosorbent assay.
    Author: Kohsaka H, Taniguchi A, Chen PP, Ollier WE, Carson DA.
    Journal: Eur J Immunol; 1993 Aug; 23(8):1895-901. PubMed ID: 8344352.
    Abstract:
    Because of heterogeneity in the outbred human population, it has been difficult to determine the genetic factors that influence the expressed T cell receptor (TcR) repertoire in autoimmune diseases. To overcome this problem, we have developed a combination of anchored polymerase chain reaction (APCR) and enzyme-linked immunosorbent assay (ELISA) that can accurately assess TcR V gene frequencies in numerous clinical samples. The results are independent of amplification efficiency, and V gene usage can be readily analyzed with an ELISA plate reader and associated software. Using this method, the TcR V beta gene repertoires in peripheral lymphocytes from nine sets of identical twins, normal, concordant or discordant for rheumatoid arthritis (RA), were studied. The TcR V beta results were compared with TcR V gamma frequencies in the same specimens as determined by APCR-ELISA and cDNA sequence analysis. The results showed a marked similarity in the TcR V beta gene repertoires between identical twins, compared to unrelated subjects (p < 0.05) whether or not they were concordant or discordant for RA. In contrast, the TcR V gamma gene repertoires in the monozygotic twins differed as much as in controls. The data imply that (a) the human TcR V beta gene repertoire in peripheral blood is genetically controlled, whereas (b) the TcR V gamma gene repertoire is primarily influenced by environmental stimuli, and (c) RA causes no consistent change in TcR V beta repertoire of peripheral blood. The APCR-ELISA method, in the context of large-scale family and population studies, should facilitate a more precise delineation of the genetic factors that regulate human TcR V beta expression.
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