DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation
Allogeneic stem cell transplantation (alloSCT) provides a curative treatment option for hematological malignancies. After HLA-matched alloSCT, donor-derived T cells recognize minor histocompatibility antigens (MiHAs), which are polymorphic peptides presented by HLA on patient cells. MiHAs are absent...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/12/e009564.full |
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| author | Sine R Hadrup Marieke Griffioen J H Frederik Falkenburg Mirjam H M Heemskerk Marian van de Meent Michel G D Kester Kyra J Fuchs Marcus Göransson Natasja W Ettienne Rob C M de Jong Eva A S Koster Constantijn J M Halkes Ferenc Scheeren Peter van Balen |
| author_facet | Sine R Hadrup Marieke Griffioen J H Frederik Falkenburg Mirjam H M Heemskerk Marian van de Meent Michel G D Kester Kyra J Fuchs Marcus Göransson Natasja W Ettienne Rob C M de Jong Eva A S Koster Constantijn J M Halkes Ferenc Scheeren Peter van Balen |
| author_sort | Sine R Hadrup |
| collection | DOAJ |
| description | Allogeneic stem cell transplantation (alloSCT) provides a curative treatment option for hematological malignancies. After HLA-matched alloSCT, donor-derived T cells recognize minor histocompatibility antigens (MiHAs), which are polymorphic peptides presented by HLA on patient cells. MiHAs are absent on donor cells due to genetic differences between patient and donor. T cells targeting broadly expressed MiHAs induce graft-versus-leukemia (GvL) reactivity as well as graft-versus-host disease (GvHD), while T cells for MiHAs with restricted or preferential expression on hematopoietic or non-hematopoietic cells may skew responses toward GvL or GvHD, respectively. Besides tissue expression, overall strength of GvL and GvHD is also determined by T-cell frequencies against MiHAs.Here, we explored the use of DNA barcode-labeled peptide-MHC multimers to detect and monitor antigen-specific T cells for the recently expanded repertoire of HLA-I-restricted MiHAs. In 16 patients who experienced an immune response after donor lymphocyte infusion, variable T-cell frequencies up to 30.5% of CD8+ T cells were measured for 49 MiHAs. High T-cell frequencies above 1% were measured in 12 patients for 19 MiHAs, with the majority directed against mismatched MiHAs, typically 6–8 weeks after donor lymphocyte infusion and at the onset of GvHD. The 12 patients included 9 of 10 patients with severe GvHD, 2 of 3 patients with limited GvHD and 1 of 3 patients without GvHD.In conclusion, we demonstrated that barcoded peptide-MHC multimers reliably detect and allow monitoring for MiHA-specific T cells during treatment to investigate the kinetics of immune responses and their impact on development of GvL and GvHD after HLA-matched alloSCT. |
| format | Article |
| id | doaj-art-5ad0d9de316d4c61a49201b465e22f42 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-5ad0d9de316d4c61a49201b465e22f422025-08-20T02:36:50ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-12-01121210.1136/jitc-2024-009564DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantationSine R Hadrup0Marieke Griffioen1J H Frederik Falkenburg2Mirjam H M Heemskerk3Marian van de Meent4Michel G D Kester5Kyra J Fuchs6Marcus Göransson7Natasja W Ettienne8Rob C M de Jong9Eva A S Koster10Constantijn J M Halkes11Ferenc Scheeren12Peter van Balen13Department of Health Technology, Technical University of Denmark, Lyngby, DenmarkDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Health Technology, Technical University of Denmark, Lyngby, DenmarkDepartment of Health Technology, Technical University of Denmark, Lyngby, DenmarkDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Dermatology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsAllogeneic stem cell transplantation (alloSCT) provides a curative treatment option for hematological malignancies. After HLA-matched alloSCT, donor-derived T cells recognize minor histocompatibility antigens (MiHAs), which are polymorphic peptides presented by HLA on patient cells. MiHAs are absent on donor cells due to genetic differences between patient and donor. T cells targeting broadly expressed MiHAs induce graft-versus-leukemia (GvL) reactivity as well as graft-versus-host disease (GvHD), while T cells for MiHAs with restricted or preferential expression on hematopoietic or non-hematopoietic cells may skew responses toward GvL or GvHD, respectively. Besides tissue expression, overall strength of GvL and GvHD is also determined by T-cell frequencies against MiHAs.Here, we explored the use of DNA barcode-labeled peptide-MHC multimers to detect and monitor antigen-specific T cells for the recently expanded repertoire of HLA-I-restricted MiHAs. In 16 patients who experienced an immune response after donor lymphocyte infusion, variable T-cell frequencies up to 30.5% of CD8+ T cells were measured for 49 MiHAs. High T-cell frequencies above 1% were measured in 12 patients for 19 MiHAs, with the majority directed against mismatched MiHAs, typically 6–8 weeks after donor lymphocyte infusion and at the onset of GvHD. The 12 patients included 9 of 10 patients with severe GvHD, 2 of 3 patients with limited GvHD and 1 of 3 patients without GvHD.In conclusion, we demonstrated that barcoded peptide-MHC multimers reliably detect and allow monitoring for MiHA-specific T cells during treatment to investigate the kinetics of immune responses and their impact on development of GvL and GvHD after HLA-matched alloSCT.https://jitc.bmj.com/content/12/12/e009564.full |
| spellingShingle | Sine R Hadrup Marieke Griffioen J H Frederik Falkenburg Mirjam H M Heemskerk Marian van de Meent Michel G D Kester Kyra J Fuchs Marcus Göransson Natasja W Ettienne Rob C M de Jong Eva A S Koster Constantijn J M Halkes Ferenc Scheeren Peter van Balen DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation Journal for ImmunoTherapy of Cancer |
| title | DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation |
| title_full | DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation |
| title_fullStr | DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation |
| title_full_unstemmed | DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation |
| title_short | DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation |
| title_sort | dna barcoded peptide mhc multimers to measure and monitor minor histocompatibility antigen specific t cells after allogeneic stem cell transplantation |
| url | https://jitc.bmj.com/content/12/12/e009564.full |
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