HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by York, I. A. Articles by Rock, K. L. Search for Related Content PubMed PubMed Citation Articles by York, I. A. Articles by Rock, K. L.

A Mutant Cell with a Novel Defect in MHC Class I Quality Control¹

Ian A. York^2,*, Ethan P. Grant^3,, A. Maria Dahl^4, and Kenneth L. Rock^*

^* Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655; and Dana-Farber Cancer Institute, Boston, MA 02115

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 (5% of parental levels) was identified. This cell line synthesized normal levels of the MHC class I H chain and 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 ₂-microglobulin failed to associate to form the normal peptide-receptive complex. In contrast, mouse H chains associated with 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.

This article has been cited by other articles:

				A. Hearn, I. A. York, and K. L. Rock The Specificity of Trimming of MHC Class I-Presented Peptides in the Endoplasmic Reticulum J. Immunol., November 1, 2009; 183(9): 5526 - 5536. [Abstract] [Full Text] [PDF]