Class II-associated invariant chain peptide-independent binding of invariant chain to class II MHC molecules.
J Immunol
; 162(3): 1502-9, 1999 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-9973407
The class II-associated invariant chain peptide (CLIP) region of invariant chain (Ii) is believed to play a critical role in the assembly and transport of MHC class II alphabetaIi 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 alphabetaIi. 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 alphabeta peptide-binding groove. We conclude that strong interactions involving Ii(103-118) and other regions of Ii cooperate in the assembly of functional alphabetaIi 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Diferenciação de Linfócitos B
/
Antígenos de Histocompatibilidade Classe II
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos