Human leukocyte antigen B*57:01 (HLA-B*57:01) (HLA-B*57:01)

The HLA-B*57:01 peptide-binding groove is a specialized structural domain of the Human Leukocyte Antigen B*57:01 molecule, a member of the Major Histocompatibility Complex (MHC) Class I family. Its primary biological function is to bind intracellularly derived peptides and present them on the cell surface for recognition by CD8+ cytotoxic T lymphocytes, thereby initiating an adaptive immune response (Migueles et al., 2000). In the context of HIV-1 infection, this specific groove is highly efficient at presenting conserved viral epitopes, such as the Gag-derived peptide TSTLQEQIGW, which is strongly associated with 'elite control' of the virus and delayed disease progression (Migueles et al., 2000). However, HLA-B*57:01 is also the critical determinant for abacavir hypersensitivity syndrome, a potentially fatal multi-organ reaction (Mallal et al., 2008). The mechanism involves the drug abacavir binding directly within the F-pocket of the groove, which alters the repertoire of self-peptides presented to the immune system (Illing et al., 2012; Ostrov et al., 2012). This 'altered self' presentation triggers a massive activation of T cells, necessitating mandatory genetic screening for the HLA-B*57:01 allele before prescribing abacavir (Mallal et al., 2008).

Other names

MHC class I antigen B*57:01HLA-B57HLA-B*5701Major histocompatibility complex, class I, B*57:01HLA-B*57:01 peptide-binding groove

Abacavir binds non-covalently to the F-pocket of the HLA-B*57:01 peptide-binding groove, altering the chemical environment and shape of the groove. This change shifts the repertoire of self-peptides presented to CD8+ T cells, leading to the recognition of 'altered self' and a systemic inflammatory response (Illing et al., 2012; Ostrov et al., 2012).