The Journal of Experimental Medicine
for flow cytometry > invitrogen
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 4 June 2001.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 101K)
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 CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McAdam, S. N.
Right arrow Articles by Sollid, L. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McAdam, S. N.
Right arrow Articles by Sollid, L. M.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/2001/6/1239/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 11, June 4, 2001 1239-1246

Original Article

T Cell Recognition of the Dominant I-Ak–Restricted Hen Egg Lysozyme Epitope: Critical Role for Asparagine Deamidation



Stephen N. McAdama, Burkhard Fleckensteinb, Ingunn B. Rasmussenc, Dietmar G. Schmidb, Inger Sandliec, Bjarne Bogena, Nicholas J. Vinerd, and Ludvig M. Sollida

a Institute of Immunology, University of Oslo, Rikshospitalet, Oslo N-0027, Norway
b Institute of Organic Chemistry University of Tübingen, 72076 Tübingen, Germany
c Department of Biology, University of Oslo, Oslo N0316, Norway
d Department of Pathology and Microbiology, University of Bristol Medical School, Bristol BS8 1TD, United Kingdom
Institute of Immunology, University of Oslo, Rikshospitalet, Oslo N-0027, Norway.47-2307-351047-2307-1374

stephen.mcadam{at}labmed.uio.no

Type-B T cells raised against the immunodominant peptide in hen egg lysozyme (HEL48–62) do not respond to whole lysozyme, and this has been thought to indicate that peptide can bind to l-Ak in different conformations. Here we demonstrate that such T cells recognize a deamidated form of the HEL peptide and not the native peptide. The sequence of the HEL epitope facilitates rapid and spontaneous deamidation when present as a free peptide or within a flexible domain. However, this deamidated epitope is not created within intact lysozyme, most likely because it resides in a highly structured part of the protein. These findings argue against the existence of multiple conformations of the same peptide–MHC complex and have important implications for the design of peptide-based vaccines. Furthermore, as the type-B T cells are known to selectively evade induction of tolerance when HEL is expressed as a transgene, these results suggest that recognition of posttranslationally modified self-antigen may play a role in autoimmunity.

Key Words: posttranslational/chemical modification • autoimmunity • peptide • deamidation • T cell

Abbreviations used in this paper: ESI, electrospray ionization; FTICR-MS, Fourier transform ion cyclotron resonance mass spectrometry; HEL, hen egg lysozyme.

© 2001 The Rockefeller University Press


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




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