title: A novel costimulatory signaling in human T lymphocytes by a splice variant of CD28.
abstract: We have characterized a splice variant (isoform) of the human CD28 T cell costimulatory receptor. The nucleotide sequence of this CD28 isoform was identical to that of CD28 in the signal peptide, the transmembrane domain, and the cytoplasmic tail, but it was missing a large segment of the extracellular ligand-binding domain, which is encoded by the second exon. This isoform (CD28i), whose message level exceeded 25% of CD28, was a transmembrane homodimer. CD28i was found noncovalently associated with CD28 and was tyrosine-phosphorylated/PI3-kinase-complexed following the crosslinking of CD28, and the CD28 costimulatory signal was enhanced in T cells expressing CD28i. These data demonstrate that CD28i, via noncovalent association with CD28, plays a role as a costimulatory signal amplifier in human T cells.
authors.affiliation: Department of Microbiology and Immunology, The John P. Robarts Research Institute, University of Western Ontario, 1400 Western Road, London, Ontario, Canada N6G 2V4.
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Yong
authors.initials: Y
authors.lastname: Ma
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Mikolajczak
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Charles
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoshida
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yoshida
authors.forename: Craig A
authors.initials: CA
authors.lastname: Strathdee
authors.forename: David W
authors.initials: DW
authors.lastname: Litchfield
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ochi
mesh_terms: D017398:Alternative Splicing / Q000276:immunology*; D001483:Base Sequence; D001665:Binding Sites; D018106:CD28 Antigens / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017384:Sequence Deletion; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015533:Transcriptional Activation
chemical_list: D018106:CD28 Antigens; D020033:Protein Isoforms; D019869:Phosphatidylinositol 3-Kinases