The Binding of Antigenic Peptides to HLA-DR Is Influenced by Interactions between Pocket 6 and Pocket 9

  • James E
  • Moustakas A
  • Bui J
  • et al.
27Citations
Citations of this article
40Readers
Mendeley users who have this article in their library.

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 β9Lys. 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 β9Lys residue is unique to DR9 alleles. However, similar studies with doubly substituted peptides confirmed an analogous interaction effect for DRA1/B1*0301, a β9Glu 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.

Cite

CITATION STYLE

APA

James, E. A., Moustakas, A. K., Bui, J., Nouv, R., Papadopoulos, G. K., & Kwok, W. W. (2009). The Binding of Antigenic Peptides to HLA-DR Is Influenced by Interactions between Pocket 6 and Pocket 9. The Journal of Immunology, 183(5), 3249–3258. https://doi.org/10.4049/jimmunol.0802228

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free