The altered peptide repertoire model of abacavir hypersensitivity.
Crystal structure of the abacavir-MHC-peptide complex shown to resolution of 0.2
nm (nanometers). a
HLA-B*57:01 is shown in gray, peptide V is
shown in cyan, and abacavir is shown as a multicolored
structure (spheres with orange for carbon,
blue for nitrogen, and red for oxygen).
b Abacavir binding leads to altered peptide repertoire by
changing the conformation of the peptide backbone in the main chain of
HLA-B*57:01. Binding of peptide is shown in the absence of
abacavir (yellow) and associated with abacavir and
HLA-B*57:01 (cyan). c H-bound
interactions (black dashes) are shown between abacavir,
peptide, and HLA-B*57:01. Specific residues differentiating for
abacavir-sensitive HLA-B*57:01 from abacavir-insensitive
HLA-B*57:03 are shown in magenta (carbon),
blue (nitrogen), and red (oxygen).
d Experimental electron density showing abacavir in a Fo-Fc
difference map with blue mesh showing the final 2Fo-Fc electron
density map of abacavir in the antigen-binding cleft of
HLA-B*57:01. H-bond interactions between abacavir and
HLA-B*57:01 are shown in yellow. (Adapted
from Ostrov et al. [14])