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. 1988 Jul;85(13):4847–4851. doi: 10.1073/pnas.85.13.4847

Cytoplasmic domain affects membrane expression and function of an Ia molecule.

I J Griffith 1, Z Ghogawala 1, N Nabavi 1, D E Golan 1, A Myer 1, D J McKean 1, L H Glimcher 1
PMCID: PMC280533  PMID: 2838848

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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