The Journal of Experimental Medicine
FluoroSpot from Mabtech
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 24 September 2001. doi:10.1084/jem.194.7.883
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 133K)
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 Sasada, T.
Right arrow Articles by Reinherz, E. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sasada, T.
Right arrow Articles by Reinherz, E. L.
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?
© The Rockefeller University Press, 0022-1007/2001/10/883/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 7, October 1, 2001 883-892

Original Article

A Naturally Processed Mitochondrial Self-Peptide in Complex with Thymic MHC Molecules Functions as a Selecting Ligand for a Viral-specific T Cell Receptor

Tetsuro Sasadaa, Yoseph Ghendlera, John M. Neveub, William S. Laneb, and Ellis L. Reinherza
a Laboratory of Immunobiology and Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115
b Microchemistry and Proteomics Analysis Facility, Harvard University, Cambridge, MA 02138

Correspondence to: Ellis L. Reinherz, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Tel:617-632-3412 Fax:617-632-3351 E-mail:ellis_reinherz{at}dfci.harvard.edu.

Peptide fragments of self-proteins bound to major histocompatibility complex molecules within the thymus are important for positively selecting T cell receptor (TCR)-bearing CD4+CD8+ double positive (DP) thymocytes for further maturation. The relationship between naturally processed thymic self-peptides and TCR-specific cognate peptides is unknown. Here we employ HPLC purification of peptides released from H-2Kb molecules of the C57BL/6 thymus in conjunction with mass spectrometry (MS) and functional profiling to identify a naturally processed Kb-bound peptide positively selecting the N15 TCR specific for the vesicular stomatitis virus octapeptide (VSV8) bound to Kb. The selecting peptide was identified in 1 of 80 HPLC fractions and shown by tandem MS (MS/MS) sequencing to correspond to residues 68–75 of the MLRQ subunit of the widely expressed mitochondrial NADH ubiquinone oxidoreductase (NUbO68–75). Of note, the peptide differs at six of its eight residues from the cognate peptide VSV8 and functions as a weak agonist for mature CD8 single positive (SP) N15 T cells, with activity 10,000-fold less than VSV8. In N15 transgenic (tg) recombinase activating gene 2-/- transporter associated with antigen processing 1-/- fetal thymic organ culture, NUbO68–75 induces phenotypic and functional differentiation of N15 TCR bearing CD8 SP thymocytes. Failure of NUbO68–75 to support differentiation of a second Kb-restricted TCR indicates that its inductive effects are not general.

Key Words: positive selection, thymocyte development, CTL, naturally processed peptides, TAP-1-/-


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