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

The Human leukocyte antigen B*57:01–HIV peptide complex is a specific molecular assembly consisting of the HLA-B*57:01 protein, a beta-2 microglobulin subunit, and an immunogenic peptide derived from the Human Immunodeficiency Virus (HIV) [4, 5]. This complex plays a pivotal role in the immune system's ability to recognize and eliminate HIV-infected cells by presenting viral antigens to CD8+ cytotoxic T lymphocytes [5]. Clinically, the HLA-B*57:01 allele is strongly associated with "elite controllers," individuals who can suppress HIV replication to undetectable levels without antiretroviral therapy [4]. However, this molecule is also the primary mediator of Abacavir Hypersensitivity Syndrome (AHS), a severe adverse reaction to the reverse transcriptase inhibitor abacavir [3]. Abacavir binds non-covalently within the F-pocket of the HLA-B*57:01 binding groove, changing the repertoire of peptides presented to T cells and causing the immune system to attack self-tissues [1, 2]. This "altered repertoire" model explains how a drug can induce a polyclonal T-cell response by making self-peptides appear foreign [1]. Consequently, screening for the HLA-B*57:01 genotype is a mandatory safety biomarker in clinical practice before initiating abacavir therapy to prevent life-threatening toxicity [3]. The complex serves as a model for understanding both viral immunity and the molecular basis of idiosyncratic drug reactions. Sources: [1] Illing, P. T., et al. (2012). Nature, 486(7404), 554-558. [2] Ostrov, D. A., et al. (2012). PNAS, 109(25), 9959-9964. [3] Mallal, S., et al. (2008). NEJM, 358(6), 568-579. [4] International HIV Controllers Study (2010). Science, 330(6010), 1551-1556. [5] UniProt Consortium. HLA class I antigen B*57 alpha chain (P01889).

Other names

HLA-B*57:01MHC class I antigen B*57:01HLA-B57B*5701HLA-B*57:01-peptide complex

Abacavir binds non-covalently to the F-pocket of the HLA-B*57:01 antigen-binding cleft, altering the repertoire of presented self-peptides and triggering a polyclonal T-cell mediated immune response [1, 2].