HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Dominance of an alternative CLIP sequence in the celiac disease associated HLA-DQ2 molecule.

Abstract
During assembly, HLA class II molecules associate with the invariant chain. As the result, the peptide-binding groove is occupied by an invariant chain peptide termed CLIP (class-II-associated invariant chain peptide; sequence MRMATPLLM). By mass spectrometry, we have now characterized peptides that are naturally present in HLA-DQ2. This analysis revealed that 22 variants of Ii-derived peptides are associated with HLA-DQ2. Strikingly, the large majority of those do not contain the conventional CLIP sequence MRMATPLLM, but instead a peptide that partially overlaps with CLIP, sequence TPLLMQALPM. Peptide binding studies indicate that this alternative CLIP peptide has superior HLA-DQ2 binding properties compared to the conventional CLIP and that the minimal nine-amino-acid binding core consists of the sequence PLLMQALPM, findings that could be corroborated by molecular simulation. The alternative CLIP peptide was also found to be present in HLA-DQ2 molecules isolated from human thymus. Moreover, the alternative CLIP peptide was also found in association with HLA-DQ8. Together, these results indicate that HLA-DQ2 and HLA-DQ8 associate with an alternative CLIP sequence, a property that may relate to the strong association between HLA-DQ molecules and human autoimmune diseases.
AuthorsMartina Wiesner, Dariusz Stepniak, Arnoud H de Ru, Antonis K Moustakis, Jan W Drijfhout, George K Papadopoulos, Peter A van Veelen, Frits Koning
JournalImmunogenetics (Immunogenetics) Vol. 60 Issue 9 Pg. 551-5 (Sep 2008) ISSN: 0093-7711 [Print] United States
PMID18584168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Differentiation, B-Lymphocyte
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • Histocompatibility Antigens Class II
  • Peptides
  • invariant chain
Topics
  • Amino Acid Sequence
  • Antigens, Differentiation, B-Lymphocyte (immunology, metabolism)
  • Celiac Disease (immunology)
  • HLA-DQ Antigens (chemistry, genetics, immunology)
  • Histocompatibility Antigens Class II (immunology, metabolism)
  • Humans
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides (immunology, metabolism)
  • Protein Binding
  • Protein Conformation

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: