title: Loss of high affinity transforming growth factor-beta 1 (TGF-beta 1) binding to a nephritogenic T cell results in absence of growth inhibition by TGF-beta 1 and augmented nephritogenicity.
abstract: Transforming growth factor-beta (TGF-beta) affects cellular proliferation and differentiation and has been linked to the development of pathologic extracellular matrix production characteristic of progressive renal disease. TGF-beta 1 is conventionally regarded as having growth-inhibitory activity on T lymphocytes. The growth-regulatory activity of TGF-beta 1 depends on the interaction of TGF-beta 1 with its receptors, especially the type I and II receptors. In this study, we describe a CD4+ nephritogenic T cell clone that, unlike a sister clone with an identical TCR Ag receptor, is not growth inhibited by TGF-beta 1, nor is its nephritogenicity affected by exogenous TGF-beta 1. Although this TGF-beta-resistant T cell clone expresses both type I and II TGF-beta receptors on the cell surface, the affinity of this interaction is markedly diminished compared with that of the sister T cell clone, which does undergo growth arrest in response to extracellular TGF-beta 1. The resistant T cell clone expresses one mutant allele for the type I TGF-beta receptor. This mutation consists of a leucine to glutamine substitution at codon 122, a conserved amino acid in the transmembrane domain. We speculate that this mutation alters the interaction between the type I and II TGF-beta receptors following recognition of ligand by the type II receptor.
authors.affiliation: Department of Medicine, University of California, San Diego 92161, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Bailey
authors.forename: Y
authors.initials: Y
authors.lastname: Frishberg
authors.forename: C J
authors.initials: CJ
authors.lastname: Kelly
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000276:immunology; D002999:Clone Cells; D006131:Growth Inhibitors / Q000494:pharmacology*; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009154:Mutation; D009395:Nephritis, Interstitial / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta