3DX6

Crystal Structure of B*4402 presenting a 10mer EBV epitope

Summary for 3DX6

• Entry DOI: 10.2210/pdb3dx6/pdb
• Related: 3DX7 3DX8 3DX9 3DXA
• Descriptor: HLA class I histocompatibility complex HLA-B*4402, Beta-2-microglobulin, EBV decapeptide epitope, ... (6 entities in total)
• Functional Keywords: mhc, glycoprotein, glycation, host-virus interaction, immune response, membrane, mhc i, transmembrane, pyrrolidone carboxylic acid, disease mutation, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30481; Secreted: P61769; Host nucleus matrix: P03204
• Total number of polymer chains: 3
• Total formula weight: 45726.42

Authors

Archbold, J.K.,Ely, L.K.,Rossjohn, J. (deposition date: 2008-07-23, release date: 2009-01-27, Last modification date: 2024-10-16)

Primary citation

Archbold, J.K.,Macdonald, W.A.,Gras, S.,Ely, L.K.,Miles, J.J.,Bell, M.J.,Brennan, R.M.,Beddoe, T.,Wilce, M.C.,Clements, C.S.,Purcell, A.W.,McCluskey, J.,Burrows, S.R.,Rossjohn, J.
Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition.
J.Exp.Med., 206:209-219, 2009

PubMed Abstract: Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell-mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR-HLA-B*4405(EENLLDFVRF) complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.

PubMed: 19139173
DOI: 10.1084/jem.20082136

Experimental method

X-RAY DIFFRACTION (1.701 Å)