Naturally occurring A pocket polymorphism in HLA-B*2703 increases the dependence on an accessory anchor residue at P1 for optimal binding of nonamer peptides.
Previous studies have shown the B*2703 subtype of HLA-B27, which differs from B*2705 and other MHC class I molecules by having a His substituted for Tyr at position 59 in the A pocket, inefficiently presents certain B*2705-restricted peptides. The current work investigates the influence of the first...
| المؤلفون الرئيسيون: | , , , , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
1997
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| _version_ | 1826288107697209344 |
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| author | Griffin, T Yuan, J Friede, T Stevanovic, S Ariyoshi, K Rowland-Jones, S Rammensee, H Colbert, R |
| author_facet | Griffin, T Yuan, J Friede, T Stevanovic, S Ariyoshi, K Rowland-Jones, S Rammensee, H Colbert, R |
| author_sort | Griffin, T |
| collection | OXFORD |
| description | Previous studies have shown the B*2703 subtype of HLA-B27, which differs from B*2705 and other MHC class I molecules by having a His substituted for Tyr at position 59 in the A pocket, inefficiently presents certain B*2705-restricted peptides. The current work investigates the influence of the first peptidic amino acid (P1) on peptide binding to B*2705 and B*2703. Results show P1 has a marked effect for both subtypes, with relative affinities (EC50) of P1-substituted peptides spanning four orders of magnitude. All peptides tested bind better to B*2705 than to B*2703. However, Lys, Arg, Phe, or Trp at P1 result in a < or = 2-fold difference between subtypes, while other amino acids produce greater differences (maximum approximately 50-fold for Leu). Self peptides eluted from B*2703, as well as two viral epitopes, have a motif similar to B*2705 peptides, except for a stronger preference for Lys or Arg at P1, consistent with peptide binding data. Computer modeling of B*2703 reveals movement of a water molecule and the alpha1 alpha-helix to allow His at position 59 to maintain important hydrogen bonds with the peptide N terminus in the A pocket. However, these bonds are weaker, and the water molecule movement results in the loss of a hydrogen bond with Glu-45 in the B pocket. We conclude that B*2703, as a consequence of its unique A pocket polymorphism, appears to have a greater dependency on an accessory anchor residue at P1 to maintain tight binding of peptides. |
| first_indexed | 2024-03-07T02:08:44Z |
| format | Journal article |
| id | oxford-uuid:9fde6fcf-f342-4094-908f-530c3bcfc7ef |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:08:44Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:9fde6fcf-f342-4094-908f-530c3bcfc7ef2022-03-27T02:01:18ZNaturally occurring A pocket polymorphism in HLA-B*2703 increases the dependence on an accessory anchor residue at P1 for optimal binding of nonamer peptides.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9fde6fcf-f342-4094-908f-530c3bcfc7efEnglishSymplectic Elements at Oxford1997Griffin, TYuan, JFriede, TStevanovic, SAriyoshi, KRowland-Jones, SRammensee, HColbert, RPrevious studies have shown the B*2703 subtype of HLA-B27, which differs from B*2705 and other MHC class I molecules by having a His substituted for Tyr at position 59 in the A pocket, inefficiently presents certain B*2705-restricted peptides. The current work investigates the influence of the first peptidic amino acid (P1) on peptide binding to B*2705 and B*2703. Results show P1 has a marked effect for both subtypes, with relative affinities (EC50) of P1-substituted peptides spanning four orders of magnitude. All peptides tested bind better to B*2705 than to B*2703. However, Lys, Arg, Phe, or Trp at P1 result in a < or = 2-fold difference between subtypes, while other amino acids produce greater differences (maximum approximately 50-fold for Leu). Self peptides eluted from B*2703, as well as two viral epitopes, have a motif similar to B*2705 peptides, except for a stronger preference for Lys or Arg at P1, consistent with peptide binding data. Computer modeling of B*2703 reveals movement of a water molecule and the alpha1 alpha-helix to allow His at position 59 to maintain important hydrogen bonds with the peptide N terminus in the A pocket. However, these bonds are weaker, and the water molecule movement results in the loss of a hydrogen bond with Glu-45 in the B pocket. We conclude that B*2703, as a consequence of its unique A pocket polymorphism, appears to have a greater dependency on an accessory anchor residue at P1 to maintain tight binding of peptides. |
| spellingShingle | Griffin, T Yuan, J Friede, T Stevanovic, S Ariyoshi, K Rowland-Jones, S Rammensee, H Colbert, R Naturally occurring A pocket polymorphism in HLA-B*2703 increases the dependence on an accessory anchor residue at P1 for optimal binding of nonamer peptides. |
| title | Naturally occurring A pocket polymorphism in HLA-B*2703 increases the dependence on an accessory anchor residue at P1 for optimal binding of nonamer peptides. |
| title_full | Naturally occurring A pocket polymorphism in HLA-B*2703 increases the dependence on an accessory anchor residue at P1 for optimal binding of nonamer peptides. |
| title_fullStr | Naturally occurring A pocket polymorphism in HLA-B*2703 increases the dependence on an accessory anchor residue at P1 for optimal binding of nonamer peptides. |
| title_full_unstemmed | Naturally occurring A pocket polymorphism in HLA-B*2703 increases the dependence on an accessory anchor residue at P1 for optimal binding of nonamer peptides. |
| title_short | Naturally occurring A pocket polymorphism in HLA-B*2703 increases the dependence on an accessory anchor residue at P1 for optimal binding of nonamer peptides. |
| title_sort | naturally occurring a pocket polymorphism in hla b 2703 increases the dependence on an accessory anchor residue at p1 for optimal binding of nonamer peptides |
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