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 Bikoff, E. K. Articles by Van Kaer, L. Search for Related Content PubMed PubMed Citation Articles by Bikoff, E. K. Articles by Van Kaer, L.

Distinct Peptide Loading Pathways for MHC Class II Molecules Associated with Alternative Ii Chain Isoforms¹

Elizabeth K. Bikoff^2,*, George Kenty^* and Luc Van Kaer

^* Department of Molecular and Cellular Biology, The Biological Laboratories, Harvard University, Cambridge, MA 02138; and Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232

Mutant mouse strains expressing either p31 or p41 Ii chain appear equally competent with respect to their class II functional activities including Ag presentation and CD4⁺ T cell development. To further explore possibly divergent roles provided by alternative Ii chain isoforms, we compare class II structure and function in double mutants also carrying a null allele at the H2-DM locus. As for DM mutants expressing wild-type Ii chain, A^bAß^b dimers present in DM-deficient mice expressing either Ii chain isoform appear equally occupied by class II-associated Ii chain-derived peptides (CLIP). Surprisingly, in functional assays, these novel mouse strains exhibit strikingly different phenotypes. Thus, DM-deficient mice expressing wild-type Ii chain or p31 alone are both severely compromised in their abilities to present peptides. In contrast, double mutants expressing the p41 isoform display markedly enhanced peptide-loading capabilities, approaching those observed for wild-type mice. The present data strengthen evidence for divergent class II presentation pathways and demonstrate for the first time that functionally distinct roles are mediated by alternatively spliced forms of the MHC class II-associated Ii chain in a physiologic setting.

This article has been cited by other articles:

				C. H. Koonce, G. Wutz, E. J. Robertson, A. B. Vogt, H. Kropshofer, and E. K. Bikoff DM Loss in k Haplotype Mice Reveals Isotype-Specific Chaperone Requirements J. Immunol., April 1, 2003; 170(7): 3751 - 3761. [Abstract] [Full Text] [PDF]

				Q. Ye, P. W. Finn, R. Sweeney, E. K. Bikoff, and R. J. Riese MHC Class II-Associated Invariant Chain Isoforms Regulate Pulmonary Immune Responses J. Immunol., February 1, 2003; 170(3): 1473 - 1480. [Abstract] [Full Text] [PDF]

				K. Honey, T. Nakagawa, C. Peters, and A. Rudensky Cathepsin L Regulates CD4+ T Cell Selection Independently of Its Effect on Invariant Chain: A Role in the Generation of Positively Selecting Peptide Ligands J. Exp. Med., May 20, 2002; 195(10): 1349 - 1358. [Abstract] [Full Text] [PDF]

				E. K. Bikoff, G. Wutz, G. A. Kenty, C. H. Koonce, and E. J. Robertson Relaxed DM Requirements During Class II Peptide Loading and CD4+ T Cell Maturation in BALB/c Mice J. Immunol., April 15, 2001; 166(8): 5087 - 5098. [Abstract] [Full Text] [PDF]