The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 19 May 2003. doi:10.1084/jem.20022226
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Seamons, A.
Right arrow Articles by Goverman, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seamons, A.
Right arrow Articles by Goverman, J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/5/1391 $5.00
The Journal of Experimental Medicine, Volume 197, Number 10, 1391-1397

Brief Definitive Report

 Competition Between Two MHC Binding Registers in a Single Peptide Processed from Myelin Basic Protein Influences Tolerance and Susceptibility to Autoimmunity

Audrey Seamons1, Jennifer Sutton4, Dina Bai4, Emily Baird2, Nena Bonn2, Björn F.C. Kafsack2, Jeffrey Shabanowitz4, Donald F. Hunt4,5, Craig Beeson2 and Joan Goverman3

1 Department of Genome Sciences, University of Washington, Seattle, WA 98125
2 Department of Chemistry, University of Washington, Seattle, WA 98125
3 Department of Immunology, University of Washington, Seattle, WA 98125
4 Department of Chemistry, University of Virginia, Charlottesville, VA 22901
5 Department of Pathology, University of Virginia, Charlottesville, VA 22901

Address correspondence to Dr. Joan Goverman, Department of Immunology, Box 357650, University of Washington, Seattle, WA 98195. Phone: 206-685-7604; Fax: 206-543-1013; E-mail: goverman{at}u.washington.edu

Experimental allergic encephalomyelitis (EAE) is an animal model for multiple sclerosis induced by stimulating myelin basic protein (MBP)-specific T cells. The MBP-specific repertoire in B10.PL mice is shaped by tolerance mechanisms that eliminate MBP121–150–specific T cells. In contrast, MBPAc1–11–specific T cells escape tolerance and constitute the encephalitogenic repertoire. To determine if this differential tolerance is caused by differences in the abundance of MBP epitopes generated by processing, MBP peptides were eluted from I-Au complexes and analyzed by mass spectrometry. Peptides were identified from both the NH2-terminal and MBP121–150 regions. Unexpectedly, MBPAc1–18 and Ac1–17, which contain the MBPAc1–11 epitope, were much more abundant than MBP121–150 peptides. The results demonstrate that competition between two I-Au binding registers, a low affinity register defined by MBPAc1–11 and a high affinity register defined by MBP5–16, prevents most of the NH2-terminal naturally processed peptides from binding in the MBPAc1–11 register. The small fraction of MBPAc1–18 bound in the MBPAc1–11 register is not sufficient to induce tolerance but provides a ligand for MBPAc1–11–specific T cells during disease. These results provide a basis for both the lack of tolerance to MBPAc1–11 and the ability of this epitope to become a target during autoimmunity.

Key Words: experimental allergic encephalomyelitis • antigen processing • T cell tolerance • MHC class II • MBP epitopes


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS