title: A reversible defect in alpha-beta T cell receptor assembly.
abstract: A human leukemia cell line, SUP-T13, can gain and lose TCR/CD3 expression at rates incompatible with spontaneous mutation. In this study, we determined (i) the generality of this phenomenon among other T cell lines, (ii) the specificity of this phenomenon to the TCR/CD3 complex, and (iii) the molecular mechanism of TCR/CD3 loss in the SUP-T13 cell line at a biochemical level. We show that two other T cell lines can undergo gain and loss of TCR/CD3 expression at similar rates. However, class I MHC molecules do not switch expression on and off, demonstrating that such switching is not an artifact of the analysis. To determine the mechanism for loss of surface TCR/CD3 expression, pulse-chase labeling and immunoprecipitation were performed on SUP-T13 TCR/CD3 negative cells. These analyses revealed that TCR alpha proteins are produced, but do not covalently associate with TCR beta-CD3 proteins in the negative cells. Thus, these variants represent a novel level of posttranslational regulation of TCR/CD3 expression, namely, the disulfide linkage of alpha and beta TCR chains.
authors.affiliation: Department of Medicine/Oncology, Stanford University Medical Center, Stanford, California 94305, USA.
authors.forename: H
authors.initials: H
authors.lastname: Maecker
authors.forename: J T
authors.initials: JT
authors.lastname: Thomas
authors.forename: R L
authors.initials: RL
authors.lastname: Consorti
authors.forename: T M
authors.initials: TM
authors.lastname: Ellis
mesh_terms: D006031:Glycosylation; D006801:Humans; D015458:Leukemia, T-Cell; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta