The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 269K)
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 Niedermann, G.
Right arrow Articles by Eichmann, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Niedermann, G.
Right arrow Articles by Eichmann, K.
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, 0022-1007/1997/7/209/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 2, July 21, 1997 209-220

Article

Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System

Gabriele Niedermann*, Rudolf Grimm{ddagger}, Elke Geier*, Martina Maurer*, Claudio Realini§, Christoph Gartmann*, Jürgen Soll||, Satoshi Omura, Martin C. Rechsteiner§, Wolfgang Baumeister**, and Klaus Eichmann*

From the * Max-Planck-Institut für Immunbiologie, 79108 Freiburg, Germany; {ddagger} Hewlett-Packard GmbH, 76337 Waldbronn, Germany; § Department of Biochemistry, University of Utah, Salt Lake City, Utah 84123; || Botanisches Institut, Universität Kiel, 24089 Kiel, Germany; The Kitasato Institute, Tokyo 108, Japan; and ** Max-Planck-Institut für Biochemie, 82152 Martiensried, Germany

To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the proteolytic fragments generated by vertebrate proteasomes have structural features in common with peptides eluted from MHC class I molecules, suggesting that many MHC class I ligands are direct products of proteasomal proteolysis. Here, we report that the processing of polypeptides by proteasomes is conserved in evolution, not only among vertebrate species, but including invertebrate eukaryotes such as insects and yeast. Unexpectedly, we found that several high copy ligands of MHC class I molecules, in particular, self-ligands, are major products in digests of source polypeptides by invertebrate proteasomes. Moreover, many major dual cleavage peptides produced by invertebrate proteasomes have the length and the NH2 and COOH termini preferred by MHC class I. Thus, the ability of proteasomes to generate potentially immunocompetent peptides evolved well before the vertebrate immune system. We demonstrate with polypeptide substrates that interferon {gamma} induction in vivo or addition of recombinant proteasome activator 28{alpha} in vitro alters proteasomal proteolysis in such a way that the generation of peptides with the structural features of MHC class I ligands is optimized. However, these changes are quantitative and do not confer qualitatively novel characteristics to proteasomal proteolysis. The data suggest that proteasomes may have influenced the evolution of MHC class I molecules.

Address correspondence to Dr. K. Eichmann, Max-Planck-Institut für Immunbiologie, Stübeweg 51, 79108 Freiburg, Germany. Phone: 49-761-51-08-541; FAX: 49-761-51-08-545: E-mail: eichmann{at}immunbio.mpg.de

C. Realini and M.C. Rechsteiner were supported by grants from the American Cancer Society and from The National Institutes of Health.

Note added in proof. While this article was in print, the x-ray structure of the yeast 20S proteasome was reported (Groll, M., L. Ditzel, J. Löwe, D. Stock, M. Botchler, H.D. Bartunik, and R. Huber. 1997. Structure of the 20S proteasome from yeast at 2.4 A resolution. Nature (Lond.). 386:463–471). The results are in excellent agreement with the length distribution of proteasomal fragments and with the alterations by IFN-{gamma}–inducible elements described in this paper.

1Abbreviations used in this paper: β2m, β2 microglobulin; aa, amino acid; BTG1, B cell translocation gene 1; Db, H-2Db; hsp, heat shock protein; Kb, H-2Kb; LLnL, N-acetyl-L-leucinyl-L-Leucinal-L-norleucinal; MALDI-Tof-MS, matrix-assisted laser desorption/ionization time of flight mass spectrometry; PA, proteasome activator; SSU, small subunit; TAP, transporter associated with antigen processing.


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?


This article has been cited by other articles:



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