title: Cytoplasmic domain affects membrane expression and function of an Ia molecule.
abstract: The association of foreign antigen with Ia molecules on the surface of antigen-presenting cells is necessary for the interaction with the clonally distributed antigen receptor on T cells and is therefore critical in the initiation and regulation of immune responses. Ia polypeptides (alpha and beta) are composed of two extracellular domains, a transmembrane domain and a cytoplasmic domain. Although exon-shuffling experiments have demonstrated that antigen associates with the NH2-terminal alpha 1 and beta 1 domains, the roles that the other domains play in Ia function are still poorly understood. The B-hybridoma cell line 2B1 was selected in a series of positive and negative immunoselection steps for a mutation in the Ek alpha polypeptide. It was found to fortuitously contain a mutation in the Ak alpha polypeptide as well. Sequence analysis of the Ak alpha gene showed that a single base transition (C----T) resulted in a stop codon at amino acid residue 222. This caused the loss of 12 amino acids from the cytoplasmic domain of the mature polypeptide. This mutation results in a decreased level of Ak alpha polypeptide expression on the cell surface (50% of wild-type levels), an increased half-life of Ak alpha polypeptide in the cell, and a specific limited defect in antigen presentation.
authors.affiliation: Department of Cancer Biology, Harvard School of Public Health, Boston, MA.
authors.forename: I J
authors.initials: IJ
authors.lastname: Griffith
authors.forename: Z
authors.initials: Z
authors.lastname: Ghogawala
authors.forename: N
authors.initials: N
authors.lastname: Nabavi
authors.forename: D E
authors.initials: DE
authors.lastname: Golan
authors.forename: A
authors.initials: A
authors.lastname: Myer
authors.forename: D J
authors.initials: DJ
authors.lastname: McKean
authors.forename: L H
authors.initials: LH
authors.lastname: Glimcher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D000949:Histocompatibility Antigens Class II; D004247:DNA