RESUMEN
Recent studies in mice have highlighted the importance of polymorphic genetic loci such as the major histocompatibility complex (MHC) or minor lymphocyte-stimulating antigen (Mls) in determining the nature of the peripheral T-cell receptor (TcR) population. As our knowledge of the equivalent process in humans is incomplete, we have utilized a modification of the polymerase chain reaction (PCR) to determine the overall genetic contribution to the normal human TcR variable V beta gene repertoire. These data demonstrate that the normal human T-cell population contains members of all the major TcR V beta families and that there is considerable variation in the relative amounts of specific TcR V beta transcripts between individuals. We have established that the normal peripheral TcR V beta repertoire is more concordant in identical twins than in unrelated individuals. The relative importance of genetic factors in determining the peripheral TcR repertoire is emphasized by these results and suggests that, in humans, the genetic control of immune responsiveness is mediated in part by the peripheral TcR repertoire.
Asunto(s)
Variación Genética/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Gemelos Monocigóticos/genética , Adulto , Secuencia de Bases , Southern Blotting , Humanos , Región Variable de Inmunoglobulina/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Reproducibilidad de los ResultadosRESUMEN
In this paper, we have constructed deletion and deletion-insertion mutations of the chicken 5-aminolevulinate synthase 5' flanking region and examined the expression of these constructs in microinjected Xenopus oocytes. Utilising this assay, we have delimited the boundary of the 5' flanking region required for expression to be 80 bp upstream from the transcription initiation site. A second major focus of this study has been to define the role of known putative cis-acting sequences in regulating 5-aminolevulinate synthase gene expression. Expression of the insertion-deletion mutants demonstrated that only a TATA box at position -28, and a single GC box at position -78 was necessary for expression of the 5-aminolevulinate synthase gene in Xenopus oocytes. This result is unusual in view of the current state of knowledge of the function of cis-acting sequence elements in transcriptional regulation.