3DX6: Crystal Structure Of B4402 Presenting A 10mer Ebv Epitope

Citation:
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.
PDB ID: 3DX6Download
MMDB ID: 69298
PDB Deposition Date: 2008/7/23
Updated in MMDB: 2010/12
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3DX6: trimeric; determined by author and by software (PISA)
Molecular Components in 3DX6
Label Count Molecule
Proteins (3 molecules)
1
HLA Class I Histocompatibility Complex Hla-b*4402(Gene symbol: HLA-B)
Molecule annotation
1
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
1
EBV Decapeptide Epitope
Molecule annotation
Chemicals (11 molecules)
1
9
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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