Dominance of an alternative CLIP sequence in the celiac disease associated HLA-DQ2 molecule
Φόρτωση...
Ημερομηνία
Συγγραφείς
Wiesner, M.
Stepniak, D.
de Ru, A. H.
Moustakis, A. K.
Drijfhout, J. W.
Papadopoulos, G. K.
van Veelen, P. A.
Koning, F.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Immunogenetics
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
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.
Περιγραφή
Λέξεις-κλειδιά
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
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/18584168
http://www.springerlink.com/content/w2215071175l106v/fulltext.pdf
http://www.springerlink.com/content/w2215071175l106v/fulltext.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής