In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation
Donor T cell mediated graft versus host effects (GVH) may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the HLA molecules in each donor-recipient pair undergoing stem cell transplantation (SCT). Whole exome sequencing has previously demonstrated a l...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00529/full |
| _version_ | 1818318204926164992 |
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| author | Max eJameson-Lee Vishal eKoparde Phil eGriffith Allison eScalora Juliana K Sampson Haniya eKhalid Nihar U Sheth Michael eBatalo Myrna G Serrano Catherine H Roberts Michael L Hess Gregory A Buck Michael C Neale Masoud H Manjili Amir Ahmed Toor |
| author_facet | Max eJameson-Lee Vishal eKoparde Phil eGriffith Allison eScalora Juliana K Sampson Haniya eKhalid Nihar U Sheth Michael eBatalo Myrna G Serrano Catherine H Roberts Michael L Hess Gregory A Buck Michael C Neale Masoud H Manjili Amir Ahmed Toor |
| author_sort | Max eJameson-Lee |
| collection | DOAJ |
| description | Donor T cell mediated graft versus host effects (GVH) may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the HLA molecules in each donor-recipient pair undergoing stem cell transplantation (SCT). Whole exome sequencing has previously demonstrated a large number of nonsynonymous single nucleotide polymorphisms (SNP) present in HLA-matched recipients of SCT donors (GVH direction). The nucleotide sequence flanking each of these SNPs was obtained and the amino acid sequence determined. All the possible nonameric-peptides incorporating the variant amino acid resulting from these SNPs were interrogated in-silico for their likelihood to be presented by the HLA class I molecules using the Immune Epitope Database stabilized matrix method (SMM) and NetMHCpan algorithms. The SMM algorithm predicted that a median of 18,396 peptides weakly bound HLA class I molecules in individual SCT recipients, and 2,254 peptides displayed strong binding. A similar library of presented peptides was identified when the data was interrogated using the NetMHCpan algorithm. The bioinformatic algorithm presented here demonstrates that there may be a high level of mHA variation in HLA-matched individuals, constituting an HLA-specific alloreactivity potential. |
| first_indexed | 2024-12-13T09:49:31Z |
| format | Article |
| id | doaj.art-3d263b22e15a48e8b89dc4fe8dc6ef43 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T09:49:31Z |
| publishDate | 2014-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3d263b22e15a48e8b89dc4fe8dc6ef432022-12-21T23:51:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-11-01510.3389/fimmu.2014.00529112102In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic TransplantationMax eJameson-Lee0Vishal eKoparde1Phil eGriffith2Allison eScalora3Juliana K Sampson4Haniya eKhalid5Nihar U Sheth6Michael eBatalo7Myrna G Serrano8Catherine H Roberts9Michael L Hess10Gregory A Buck11Michael C Neale12Masoud H Manjili13Amir Ahmed Toor14Virginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityVirginia Commonwealth UniversityDonor T cell mediated graft versus host effects (GVH) may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the HLA molecules in each donor-recipient pair undergoing stem cell transplantation (SCT). Whole exome sequencing has previously demonstrated a large number of nonsynonymous single nucleotide polymorphisms (SNP) present in HLA-matched recipients of SCT donors (GVH direction). The nucleotide sequence flanking each of these SNPs was obtained and the amino acid sequence determined. All the possible nonameric-peptides incorporating the variant amino acid resulting from these SNPs were interrogated in-silico for their likelihood to be presented by the HLA class I molecules using the Immune Epitope Database stabilized matrix method (SMM) and NetMHCpan algorithms. The SMM algorithm predicted that a median of 18,396 peptides weakly bound HLA class I molecules in individual SCT recipients, and 2,254 peptides displayed strong binding. A similar library of presented peptides was identified when the data was interrogated using the NetMHCpan algorithm. The bioinformatic algorithm presented here demonstrates that there may be a high level of mHA variation in HLA-matched individuals, constituting an HLA-specific alloreactivity potential.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00529/fullPeptidesexome sequencingalloreactivityallogeneic stem cell transplantationHLA-peptide binding affinity |
| spellingShingle | Max eJameson-Lee Vishal eKoparde Phil eGriffith Allison eScalora Juliana K Sampson Haniya eKhalid Nihar U Sheth Michael eBatalo Myrna G Serrano Catherine H Roberts Michael L Hess Gregory A Buck Michael C Neale Masoud H Manjili Amir Ahmed Toor In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation Frontiers in Immunology Peptides exome sequencing alloreactivity allogeneic stem cell transplantation HLA-peptide binding affinity |
| title | In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation |
| title_full | In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation |
| title_fullStr | In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation |
| title_full_unstemmed | In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation |
| title_short | In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation |
| title_sort | in silico derivation of hla specific alloreactivity potential from whole exome sequencing of stem cell transplant donors and recipients understanding the quantitative immunobiology of allogeneic transplantation |
| topic | Peptides exome sequencing alloreactivity allogeneic stem cell transplantation HLA-peptide binding affinity |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00529/full |
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