The binding of antigenic peptides to HLA-DR is influenced by interactions between pocket 6 and pocket 9.
J Immunol
; 183(5): 3249-58, 2009 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-19648278
ABSTRACT
Peptide binding to class II MHC protein is commonly viewed as a combination of discrete anchor residue preferences for pockets 1, 4, 6/7, and 9. However, previous studies have suggested cooperative effects during the peptide binding process. Investigation of the DRB1*0901 binding motif demonstrated a clear interaction between peptide binding pockets 6 and 9. In agreement with prior studies, pockets 1 and 4 exhibited clear binding preferences. Previously uncharacterized pockets 6 and 7 accommodated a wide variety of residues. However, although it was previously reported that pocket 9 is completely permissive, several substitutions at this position were unable to bind. Structural modeling revealed a probable interaction between pockets 6 and 9 through beta9Lys. Additional binding studies with doubly substituted peptides confirmed that the amino acid bound within pocket 6 profoundly influences the binding preferences for pocket 9 of DRB1*0901, causing complete permissiveness of pocket 9 when a small polar residue is anchored in pocket 6 but accepting relatively few residues when a basic residue is anchored in pocket 6. The beta9Lys residue is unique to DR9 alleles. However, similar studies with doubly substituted peptides confirmed an analogous interaction effect for DRA1/B1*0301, a beta9Glu allele. Accounting for this interaction resulted in improved epitope prediction. These findings provide a structural explanation for observations that an amino acid in one pocket can influence binding elsewhere in the MHC class II peptide binding groove.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Antígenos HLA-DR
/
Antígeno HLA-DR3
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos