Class II-associated invariant chain peptide-independent binding of invariant chain to class II MHC molecules

Wesley P. Thayer, Leszek Ignatowicz, Dominique A. Weber, Peter E. Jensen

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The class II-associated in variant chain peptide (CLIP) region of invariant chain (Ii) is believed to play a critical role in the assembly and transport of MHC class II αβIi complexes through its interaction with the class II peptide-binding site. The role of the CLIP sequence was investigated by using mutant Ii molecules with altered affinity for the DR1 peptide- binding site. Both high- and low-affinity mutants were observed to efficiently assemble with DR1 and mediate transport to endosomal compartments in COS cell transfectants. Using N- and C-terminal truncations, a region adjacent to CLIP within Ii(103-118) was identified that can complement loss of affinity for the peptide-binding site in mediating efficient assembly of αβIi. A C-terminal fragment completely lacking the CLIP region, Ii(103- 216), was observed binding stably to class II molecules in immunoprecipitation studies and experiments with purified proteins. The Ii(103-118) region was required for this binding, which occurs through interactions outside of the αβ peptide-binding groove. We conclude that strong interactions involving Ii(103-118) and other regions of Ii cooperate in the assembly of functional αβIi under conditions where CLIP has little or no affinity for the class II peptide-binding site. Our results support the hypothesis that the CLIP sequence has evolved to avoid high-stability interactions with the peptide-binding sites of MHC class II molecules rather than as a promiscuous binder with moderate affinity for all class II molecules.

Original languageEnglish (US)
Pages (from-to)1502-1509
Number of pages8
JournalJournal of Immunology
Volume162
Issue number3
StatePublished - Feb 1 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Thayer, W. P., Ignatowicz, L., Weber, D. A., & Jensen, P. E. (1999). Class II-associated invariant chain peptide-independent binding of invariant chain to class II MHC molecules. Journal of Immunology, 162(3), 1502-1509.