The Journal of Immunology, Vol 156, Issue 5 1841-1847, Copyright © 1996 by American Association of Immunologists

ARTICLES

A mannose 6-phosphate-containing N-linked glycopeptide derived from lysosomal acid lipase is bound to MHC class II in B lymphoblastoid cell lines

ML Dustin, DW McCourt and S Kornfeld
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Binding of peptides to MHC class II Ag generates ligands for TCR of Th lymphocytes. We have identified a novel class of peptides bound to MHC class II: mannose 6- phosphate (Man-6-P) containing glycopeptides from lysosomal enzymes. These species were identified in the process of characterizing mannose 6-phosphate/insulin-like growth factor II (M-6- P/IGF-II) receptor binding to the surface of B lymphoblasts. Surface iodination and Man-6-P/IGF-II receptor affinity chromatography implicated MHC class II as a carrier of Man-6-P-modified oligosaccharides. These oligosaccharides were found to be primarily associated with the bound peptide. Peptides eluted from the Man-6-P/IGF- II receptor-binding fraction of immunoaffinity-purified MHC class II from the Swei cell line contained a sequence derived from the propiece of lysosomal acid lipase. Partial sequences were also obtained for peptides from other HLA-DR alleles but none of these were attributable to known proteins. This study defines a novel approach for isolating rare glycan-modified peptides from MHC class II and demonstrates that very large secondary modifications are tolerated in peptides bound to MHC class II.

This article has been cited by other articles:

				O. Zschenker, C. Bahr, U.-F. Hess, and D. Ameis Systematic Mutagenesis of Potential Glycosylation Sites of Lysosomal Acid Lipase J. Biochem., March 1, 2005; 137(3): 387 - 394. [Abstract] [Full Text] [PDF]