Cytoplasmic Domain Affects Membrane Expression and Function of an Ia Molecule
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 (α and β ) are co...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 85; no. 13; pp. 4847 - 4851 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington, DC
National Academy of Sciences of the United States of America
01.07.1988
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | 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 (α and β ) 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 α 1 and β 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 Eβk polypeptide. It was found to fortuitously contain a mutation in the Aαk polypeptide as well. Sequence analysis of the Aαk 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 Aαk polypeptide expression on the cell surface (50% of wild-type levels), an increased half-life of Aαk polypeptide in the cell, and a specific limited defect in antigen presentation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.85.13.4847 |