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PDBsum entry 3dx7
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Immune system
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PDB id
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3dx7
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References listed in PDB file
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Key reference
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Title
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Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition.
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Authors
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J.K.Archbold,
W.A.Macdonald,
S.Gras,
L.K.Ely,
J.J.Miles,
M.J.Bell,
R.M.Brennan,
T.Beddoe,
M.C.Wilce,
C.S.Clements,
A.W.Purcell,
J.Mccluskey,
S.R.Burrows,
J.Rossjohn.
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Ref.
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J Exp Med, 2009,
206,
209-219.
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PubMed id
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Abstract
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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.
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