Title

A mutant cell with a novel defect in MHC class I quality control

PubMed ID

15905525

UMMS Affiliation

Department of Pathology

Date

5-21-2005

Document Type

Article

Subjects

Animals; COS Cells; Cell Membrane; Cercopithecus aethiops; Down-Regulation; Endoplasmic Reticulum; H-2 Antigens; Humans; Mice; Molecular Chaperones; *Mutagenesis; Protein Processing, Post-Translational; Quality Control; beta 2-Microglobulin

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

COS7 (African Green Monkey kidney) cells stably transfected with the mouse MHC class I allele H-2K(b) were mutagenized, selected for low surface expression of endogenous MHC class I products, and subcloned. A mutant cell line, 4S8.12, expressing very low surface MHC class I (approximately 5% of parental levels) was identified. This cell line synthesized normal levels of the MHC class I H chain and beta(2)-microglobulin, as well as normal levels of TAP, tapasin, GRP78, calnexin, calreticulin, ERp57, and protein disulfide isomerase. Full-length OVA was processed to generate presented H-2K(b)-SIINFEKL complexes with equal efficiency in wild-type and mutant cells, demonstrating that proteasomes, as well as TAP and tapasin, functioned normally. Therefore, all the known components of the MHC class I Ag presentation pathway were intact. Nevertheless, primate (human and monkey) MHC class I H chain and beta(2)-microglobulin failed to associate to form the normal peptide-receptive complex. In contrast, mouse H chains associated with beta(2)-microglobulin normally and bound peptide at least as well as in wild-type cells. The 4S8.12 cells provide strong genetic evidence for a novel component in the MHC class I pathway. This as-yet unidentified gene is important in early assembly of primate, but not mouse, MHC class I complexes.

Rights and Permissions

Citation: J Immunol. 2005 Jun 1;174(11):6839-46.

Related Resources

Link to Article in PubMed