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PDBsum entry 2axf
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Immune system/gene regulation
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PDB id
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2axf
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References listed in PDB file
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Key reference
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Title
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The immunogenicity of a viral cytotoxic t cell epitope is controlled by its mhc-Bound conformation.
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Authors
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F.E.Tynan,
D.Elhassen,
A.W.Purcell,
J.M.Burrows,
N.A.Borg,
J.J.Miles,
N.A.Williamson,
K.J.Green,
J.Tellam,
L.Kjer-Nielsen,
J.Mccluskey,
J.Rossjohn,
S.R.Burrows.
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Ref.
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J Exp Med, 2005,
202,
1249-1260.
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PubMed id
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Abstract
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Thousands of potentially antigenic peptides are encoded by an infecting
pathogen; however, only a small proportion induce measurable CD8(+) T cell
responses. To investigate the factors that control peptide immunogenicity, we
have examined the cytotoxic T lymphocyte (CTL) response to a previously
undefined epitope ((77)APQPAPENAY(86)) from the BZLF1 protein of Epstein-Barr
virus (EBV). This peptide binds well to two human histocompatibility leukocyte
antigen (HLA) allotypes, HLA-B*3501 and HLA-B*3508, which differ by a single
amino acid at position 156 ((156)Leucine vs. (156)Arginine, respectively).
Surprisingly, only individuals expressing HLA-B*3508 show evidence of a CTL
response to the (77)APQPAPENAY(86) epitope even though EBV-infected cells
expressing HLA-B*3501 process and present similar amounts of peptide for CTL
recognition, suggesting that factors other than peptide presentation levels are
influencing immunogenicity. Functional and structural analysis revealed marked
conformational differences in the peptide, when bound to each HLA-B35 allotype,
that are dictated by the polymorphic HLA residue 156 and that directly affected
T cell receptor recognition. These data indicate that the immunogenicity of an
antigenic peptide is influenced not only by how well the peptide binds to major
histocompatibility complex (MHC) molecules but also by its bound conformation.
It also illustrates a novel mechanism through which MHC polymorphism can further
diversify the immune response to infecting pathogens.
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