Human leukocyte antigen B*57:01–VANALAHKY peptide complex (HLA-B*57:01–VANALAHKY)

The HLA-B*57:01–VANALAHKY peptide complex is a specific molecular assembly that plays a central role in the development of abacavir hypersensitivity syndrome (AHS). HLA-B*57:01 is a variant of the human leukocyte antigen B (MHC class I) protein that normally presents a specific repertoire of endogenous peptides to the immune system to maintain tolerance. However, the antiretroviral drug abacavir can bind non-covalently to the F-pocket of the HLA-B*57:01 antigen-binding groove, which changes the chemical environment and shape of the pocket (Illing et al., 2012, Nature). This modification shifts the repertoire of peptides that can be presented, allowing the binding of self-peptides like VANALAHKY (derived from the 60S ribosomal protein L23a) that would otherwise not be displayed (Norcross et al., 2012, PNAS). The resulting HLA-B*57:01–VANALAHKY complex is recognized as foreign by CD8+ T-cells, leading to a massive release of inflammatory cytokines and a systemic hypersensitivity reaction (Ostrov et al., 2012, PNAS). This interaction represents a classic example of the altered repertoire model of drug-induced autoimmunity, where a drug changes the fundamental specificity of a host immune receptor.

Other names

MHC class I B*57:01–VANALAHKY complexHLA-B*57:01–peptide complexAbacavir-HLA-B*57:01-peptide complex

Abacavir binds to the F-pocket of the HLA-B*57:01 molecule, altering the peptide-binding specificity and allowing the presentation of self-peptides like VANALAHKY, which triggers a CD8+ T-cell response.