2RFX

Crystal Structure of HLA-B*5701, presenting the self peptide, LSSPVTKSF

Summary for 2RFX

• Entry DOI: 10.2210/pdb2rfx/pdb
• Related: 2bvo 2bvp 2bvq 2hjk 2hjl
• Descriptor: HLA class I histocompatibility antigen, B-57 alpha chain, Beta-2-microglobulin, LSSPVTKSF, ... (5 entities in total)
• Functional Keywords: alpha beta sandwich-immunologlobulin like, glycoprotein, host-virus interaction, immune response, membrane, mhc i, transmembrane, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P18465; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 3
• Total formula weight: 44721.70

Authors

Archbold, J.K.,Macdonald, W.A.,Rossjohn, J.,McCluskey, J. (deposition date: 2007-10-02, release date: 2008-07-08, Last modification date: 2024-10-30)

Primary citation

Chessman, D.,Kostenko, L.,Lethborg, T.,Purcell, A.W.,Williamson, N.A.,Chen, Z.,Kjer-Nielsen, L.,Mifsud, N.A.,Tait, B.D.,Holdsworth, R.,Almeida, C.A.,Nolan, D.,Macdonald, W.A.,Archbold, J.K.,Kellerher, A.D.,Marriott, D.,Mallal, S.,Bharadwaj, M.,Rossjohn, J.,McCluskey, J.
Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity
Immunity, 28:822-832, 2008

PubMed Abstract: The basis for strong immunogenetic associations between particular human leukocyte antigen (HLA) class I allotypes and inflammatory conditions like Behçet's disease (HLA-B51) and ankylosing spondylitis (HLA-B27) remain mysterious. Recently, however, even stronger HLA associations are reported in drug hypersensitivities to the reverse-transcriptase inhibitor abacavir (HLA-B57), the gout prophylactic allopurinol (HLA-B58), and the antiepileptic carbamazepine (HLA-B*1502), providing a defined disease trigger and suggesting a general mechanism for these associations. We show that systemic reactions to abacavir were driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells. Recognition of abacavir required the transporter associated with antigen presentation and tapasin, was fixation sensitive, and was uniquely restricted by HLA-B*5701 and not closely related HLA allotypes with polymorphisms in the antigen-binding cleft. Hence, the strong association of HLA-B*5701 with abacavir hypersensitivity reflects specificity through creation of a unique ligand as well as HLA-restricted antigen presentation, suggesting a basis for the strong HLA class I-association with certain inflammatory disorders.

PubMed: 18549801
DOI: 10.1016/j.immuni.2008.04.020

Experimental method

X-RAY DIFFRACTION (2.5 Å)