Fig. 2

Abacavir-induced altered self-peptide presentation (adopted from Ostrov et al. [16] and Yun et al. [25]). a Crystal structure of a peptide, HSITYLLPV or Pep-V (cyan) bound to HLA-B*57:01 (gray) together with abacavir (shown as spheres, orange for carbon, blue for nitrogen, and red for oxygen) [16]. b Without abacavir, the HLA-B*57:01 presents the ‘normal’ self-repertoire peptides and thus does not trigger an immune response (left). In the presence of abacavir, the drug can be incorporated in the F pocket of the HLA molecule thereby altering the peptide repertoire that is loaded onto this molecule. Abacavir binding favors binding of peptides with tryptophan (W) or phenylalanine at the C-terminus (position 9) rather than the small aliphatic residues (e.g., valinine, alanine, or isoleucine) which are normally bound to unmodified HLA-B*57:01 [16, 28]. This results in recognition of neo-antigens by neo-antigen primed CD8+ T-cells (middle). On the right, a hypothetical model of how abacavir might result in the selection of shorter peptide or is recognized itself by the TCR [25].