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PDBsum entry 3mgo
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Immune system
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PDB id
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3mgo
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References listed in PDB file
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Key reference
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Title
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Identification and structural definition of h5-Specific ctl epitopes restricted by hla-A0201 Derived from the h5n1 subtype of influenza a viruses.
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Authors
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Y.Sun,
J.Liu,
M.Yang,
F.Gao,
J.Zhou,
Y.Kitamura,
B.Gao,
P.Tien,
Y.Shu,
A.Iwamoto,
Z.Chen,
G.F.Gao.
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Ref.
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J Gen Virol, 2010,
91,
919-930.
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PubMed id
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Abstract
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The haemagglutinin (HA) glycoprotein of influenza A virus is a major antigen
that initiates humoral immunity against infection; however, the cellular immune
response against HA is poorly understood. Furthermore, HA-derived cytotoxic
T-lymphocyte (CTL) epitopes are relatively rare in comparison to other internal
gene products. Here, CTL epitopes of the HA serotype H5 protein were screened.
By using in silico prediction, in vitro refolding and a T2 cell-binding assay,
followed by immunization of HLA-A2.1/K(b) transgenic mice, an
HLA-A*0201-restricted decameric epitope, RI-10 (H5 HA205-214, RLYQNPTTYI), was
shown to elicit a robust CTL epitope-specific response. In addition, RI-10 and
its variant, KI-10 (KLYQNPTTYI), were also demonstrated to be able to induce a
higher CTL epitope-specific response than the influenza A virus dominant CTL
epitope GL-9 (GILGFVFTL) in peripheral blood mononuclear cells of
HLA-A*0201-positive patients who had recovered from H5N1 virus infection.
Furthermore, the crystal structures of RI-10-HLA-A*0201 and KI-10-HLA-A*0201
complexes were determined at 2.3 and 2.2 A resolution, respectively, showing
typical HLA-A*0201-restricted epitopes. The conformations of RI-10 and KI-10 in
the antigen-presenting grooves in crystal structures of the two complexes show
significant differences, despite their nearly identical sequences. These results
provide implications for the discovery of diagnostic markers and the design of
novel influenza vaccines.
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