Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
CareStream

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 24 November 1995:
Vol. 270. no. 5240, pp. 1357 - 1359
DOI: 10.1126/science.270.5240.1357
Prev | Table of Contents | Next

Reports

Self-Release of CLIP in Peptide Loading of HLA-DR Molecules

Harald Kropshofer (1),  Anne B. Vogt (1),  Lawrence J. Stern,  Günter J. Hämmerling (2)

The assembly and transport of major histocompatibility complex (MHC) class II molecules require interaction with the invariant chain. A fragment of the invariant chain, CLIP, occupies the peptide-binding groove of the class II molecule. At endosomal pH, the binding of CLIP to human MHC class II HLA-DR molecules was counteracted by its amino-terminal segment (residues 81 to 89), which facilitated rapid release. The CLIP(81-89) fragment also catalyzed the release of CLIP(90-105) and a subset of other self-peptides, probably by transient interaction with an effector site outside the groove. Thus, CLIP may facilitate peptide loading through an allosteric release mechanism.


H. Kropshofer, A. B. Vogt, G. J. Hämmerling, Department of Molecular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
L. J. Stern, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
(1) These authors contributed equally to this work.
(2) To whom correspondence should be addressed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Dissection of the HLA-DR4 Peptide Repertoire in Endocrine Epithelial Cells: Strong Influence of Invariant Chain and HLA-DM Expression on the Nature of Ligands.
A. Muntasell, M. Carrascal, I. Alvarez, L. Serradell, P. van Veelen, F. A. W. Verreck, F. Koning, J. Abian, and D. Jaraquemada (2004)
J. Immunol. 173, 1085-1093
   Abstract »    Full Text »    PDF »
Editing of an Immunodominant Epitope of Glutamate Decarboxylase by HLA-DM.
J. D. Lich, J. A. Jayne, D. Zhou, J. F. Elliott, and J. S. Blum (2003)
J. Immunol. 171, 853-859
   Abstract »    Full Text »    PDF »
DM Loss in k Haplotype Mice Reveals Isotype-Specific Chaperone Requirements.
C. H. Koonce, G. Wutz, E. J. Robertson, A. B. Vogt, H. Kropshofer, and E. K. Bikoff (2003)
J. Immunol. 170, 3751-3761
   Abstract »    Full Text »    PDF »
Recruitment of MHC Class I Molecules by Tapasin into the Transporter Associated with Antigen Processing-Associated Complex Is Essential for Optimal Peptide Loading.
P. Tan, H. Kropshofer, O. Mandelboim, N. Bulbuc, G. J. Hammerling, and F. Momburg (2002)
J. Immunol. 168, 1950-1960
   Abstract »    Full Text »    PDF »
Relaxed DM Requirements During Class II Peptide Loading and CD4+ T Cell Maturation in BALB/c Mice.
E. K. Bikoff, G. Wutz, G. A. Kenty, C. H. Koonce, and E. J. Robertson (2001)
J. Immunol. 166, 5087-5098
   Abstract »    Full Text »    PDF »
Nonobese Diabetic Mice Display Elevated Levels of Class II-Associated Invariant Chain Peptide Associated with I-Ag7 on the Cell Surface.
A. Bhatnagar, P. J. Milburn, M. Lobigs, R. V. Blanden, and A. M. Gautam (2001)
J. Immunol. 166, 4490-4497
   Abstract »    Full Text »    PDF »
The Down-Regulation of HLA-DM Gene Expression in Rheumatoid Arthritis Is Not Related to Their Promoter Polymorphism.
P. Louis-Plence, S. Kerlan-Candon, J. Morel, B. Combe, J. Clot, V. Pinet, and J.-F. Eliaou (2000)
J. Immunol. 165, 4861-4869
   Abstract »    Full Text »    PDF »
Defensins are dominant HLA-DR-associated self-peptides from CD34- peripheral blood mononuclear cells of different tumor patients (plasmacytoma, chronic myeloid leukemia).
T. M. Halder, M. Bluggel, S. Heinzel, G. Pawelec, H. E. Meyer, and H. Kalbacher (2000)
Blood 95, 2890-2896
   Abstract »    Full Text »    PDF »
Conformational variants of class II MHC/peptide complexes induced by N- and C-terminal extensions of minimal peptide epitopes.
O. Rotzschke, K. Falk, J. Mack, J. M. Lau, G. Jung, and J. L. Strominger (1999)
PNAS 96, 7445-7450
   Abstract »    Full Text »    PDF »
Sodium Dodecyl Sulfate Stability of HLA-DR1 Complexes Correlates with Burial of Hydrophobic Residues in Pocket 1.
S. K. Natarajan, L. J. Stern, and S. Sadegh-Nasseri (1999)
J. Immunol. 162, 3463-3470
   Abstract »    Full Text »    PDF »
Class II-Associated Invariant Chain Peptide-Independent Binding of Invariant Chain to Class II MHC molecules.
W. P. Thayer, L. Ignatowicz, D. A. Weber, and P. E. Jensen (1999)
J. Immunol. 162, 1502-1509
   Abstract »    Full Text »    PDF »
In vivo priming of T cells against cryptic determinants by dendritic cells exposed to interleukin 6 and native antigen.
H. Drakesmith, D. O'Neil, S. C. Schneider, M. Binks, P. Medd, E. Sercarz, P. Beverley, and B. Chain (1998)
PNAS 95, 14903-14908
   Abstract »    Full Text »    PDF »
Antigen Processing of Two H2-IEd-Restricted Epitopes Is Differentially Influenced by the Structural Changes in a Viral Glycoprotein.
K. A. Chianese-Bullock, H. I. Russell, C. Moller, W. Gerhard, J. J. Monaco, and L. C. Eisenlohr (1998)
J. Immunol. 161, 1599-1607
   Abstract »    Full Text »    PDF »
Deficient Peptide Loading and MHC Class II Endosomal Sorting in a Human Genetic Immunodeficiency Disease: the Chediak-Higashi Syndrome.
W. Faigle, G. Raposo, D. Tenza, V. Pinet, A. B. Vogt, H. Kropshofer, A. Fischer, G. de Saint-Basile, and S. Amigorena (1998)
J. Cell Biol. 141, 1121-1134
   Abstract »    Full Text »    PDF »
Promiscuous Binding of Synthetic Copolymer 1 to Purified HLA-DR Molecules.
M. Fridkis-Hareli and J. L. Strominger (1998)
J. Immunol. 160, 4386-4397
   Abstract »    Full Text »    PDF »
Distinct Peptide Loading Pathways for MHC Class II Molecules Associated with Alternative Ii Chain Isoforms.
E. K. Bikoff, G. Kenty, and L. Van Kaer (1998)
J. Immunol. 160, 3101-3110
   Abstract »    Full Text »    PDF »
Dendritic cell maturation and antigen presentation in the absence of invariant chain.
P. Rovere, V. S. Zimmermann, F. Forquet, D. Demandolx, J. Trucy, P. Ricciardi-Castagnoli, and J. Davoust (1998)
PNAS 95, 1067-1072
   Abstract »    Full Text »    PDF »
Efficient loading of HLA-DR with a T helper epitope by genetic exchange of CLIP.
J. van Bergen, S. P. Schoenberger, F. Verreck, R. Amons, R. Offringa, and F. Koning (1997)
PNAS 94, 7499-7502
   Abstract »    Full Text »    PDF »
Enhanced Dissociation of HLA-DR-Bound Peptides in the Presence of HLA-DM.
D. A. Weber, B. D. Evavold, and P. E. Jensen (1996)
Science 274, 618-621
   Abstract »    Full Text »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)