A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A*24 Allotypes
While many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components. We investigated micropolymorphisms at position 156 of HLA-A*24 allotypes...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2014/298145 |
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| author | Soumya Badrinath Heike Kunze-Schumacher Rainer Blasczyk Trevor Huyton Christina Bade-Doeding |
| author_facet | Soumya Badrinath Heike Kunze-Schumacher Rainer Blasczyk Trevor Huyton Christina Bade-Doeding |
| author_sort | Soumya Badrinath |
| collection | DOAJ |
| description | While many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components. We investigated micropolymorphisms at position 156 of HLA-A*24 allotypes and their effects on PLC dependence for assembly and peptide binding specificities. HLA-A*24:06156Trp and HLA-A*24:13156Leu showed high levels of cell surface expression while HLA-A*24:02156Gln was expressed at low levels in tapasin deficient cells. Peptides presented by these allelic variants showed distinct differences in features and repertoire. Immunoprecipitation experiments demonstrated all the HLA-A*24/156 variants to associate at similar levels with tapasin when present. Structurally, HLA-A*24:02 contains the residue triad Met97/His114/Gln156 and a Trp156 or Leu156 polymorphism provides tapasin independence by stabilizing these triad residues, thus generating an energetically stable and a more peptide receptive environment. Micropolymorphisms at position 156 can influence the generic peptide loading pathway for HLA-A*24 by altering their tapasin dependence for peptide selection. The trade-off for this tapasin independence could be the presentation of unusual ligands by these alleles, imposing significant risk following hematopoietic stem cell transplantation (HSCT). |
| format | Article |
| id | doaj-art-59c87d2e2f814f05af8adb466d93444a |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-59c87d2e2f814f05af8adb466d93444a2025-08-20T03:34:26ZengWileyJournal of Immunology Research2314-88612314-71562014-01-01201410.1155/2014/298145298145A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A*24 AllotypesSoumya Badrinath0Heike Kunze-Schumacher1Rainer Blasczyk2Trevor Huyton3Christina Bade-Doeding4Institute for Transfusion Medicine, Hannover Medical School, Medical Park, Feodor Lynen Street 21, 30625 Hannover, GermanyInstitute for Transfusion Medicine, Hannover Medical School, Medical Park, Feodor Lynen Street 21, 30625 Hannover, GermanyInstitute for Transfusion Medicine, Hannover Medical School, Medical Park, Feodor Lynen Street 21, 30625 Hannover, GermanyInstitute for Transfusion Medicine, Hannover Medical School, Medical Park, Feodor Lynen Street 21, 30625 Hannover, GermanyInstitute for Transfusion Medicine, Hannover Medical School, Medical Park, Feodor Lynen Street 21, 30625 Hannover, GermanyWhile many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components. We investigated micropolymorphisms at position 156 of HLA-A*24 allotypes and their effects on PLC dependence for assembly and peptide binding specificities. HLA-A*24:06156Trp and HLA-A*24:13156Leu showed high levels of cell surface expression while HLA-A*24:02156Gln was expressed at low levels in tapasin deficient cells. Peptides presented by these allelic variants showed distinct differences in features and repertoire. Immunoprecipitation experiments demonstrated all the HLA-A*24/156 variants to associate at similar levels with tapasin when present. Structurally, HLA-A*24:02 contains the residue triad Met97/His114/Gln156 and a Trp156 or Leu156 polymorphism provides tapasin independence by stabilizing these triad residues, thus generating an energetically stable and a more peptide receptive environment. Micropolymorphisms at position 156 can influence the generic peptide loading pathway for HLA-A*24 by altering their tapasin dependence for peptide selection. The trade-off for this tapasin independence could be the presentation of unusual ligands by these alleles, imposing significant risk following hematopoietic stem cell transplantation (HSCT).http://dx.doi.org/10.1155/2014/298145 |
| spellingShingle | Soumya Badrinath Heike Kunze-Schumacher Rainer Blasczyk Trevor Huyton Christina Bade-Doeding A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A*24 Allotypes Journal of Immunology Research |
| title | A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A*24 Allotypes |
| title_full | A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A*24 Allotypes |
| title_fullStr | A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A*24 Allotypes |
| title_full_unstemmed | A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A*24 Allotypes |
| title_short | A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A*24 Allotypes |
| title_sort | micropolymorphism altering the residue triad 97 114 156 determines the relative levels of tapasin independence and distinct peptide profiles for hla a 24 allotypes |
| url | http://dx.doi.org/10.1155/2014/298145 |
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