Detection of Allo-HLA Cross-Reactivity by Virus-specific Memory T-Cell Clones Using Single HLA-Transfected K562 Cells

D’Orsogna, Lloyd; Meer-Prins, E.M.W. van der; Zoet, Yvonne M.; Roelen, Dave L.; Doxiadis, Ilias I.N.; Claas, Frans H.J.

doi:10.1007/978-1-61779-842-9_19

Cited by 15 publications

(13 citation statements)

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“…Virus‐specific CD8 + memory T cell clones were generated by fluorescence‐activated cell sorting (FACS; FACSAria; BD Biosciences), as described previously . PBMCs of healthy donors were stained with PE‐labeled viral tetramers CMV pp65(123‐131) HLA‐B*35:01/IPSINVHHY (CMV B35/IPS), influenza (FLU) IMP(58‐66) HLA‐A*02:01/GILGFVFTL (FLU A2/GIL), and varicella zoster virus (VZV) IE62(593‐601) HLA‐A*02:01/ALWALPHAA (VZV A2/ALW; protein facility of the Leiden University Medical Center) and fluorescein isothiocyanate–labeled mAb against CD4, CD19, CD45‐RA, CD14, CD40, CD16, and CD56 (BD Pharmingen, San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

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Allo-HLA Cross-Reactivities of Cytomegalovirus-, Influenza-, and Varicella Zoster Virus–Specific Memory T Cells Are Shared by Different Healthy Individuals

Heuvel

Heutinck

Meer-Prins

et al. 2017

American Journal of Transplantation

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Virus-specific T cells can recognize allogeneic HLA (allo-HLA) through TCR cross-reactivity. The allospecificity often differs by individual (private cross-reactivity) but also can be shared by multiple individuals (public cross-reactivity); however, only a few examples of the latter have been described. Because these could facilitate alloreactivity prediction in transplantation, we aimed to identify novel public cross-reactivities of human virus-specific CD8 T cells directed against allo-HLA by assessing their reactivity in mixed-lymphocyte reactions. Further characterization was done by studying TCR usage with primer-based DNA sequencing, cytokine production with ELISAs, and cytotoxicity with chromium-release assays. We identified three novel public allo-HLA cross-reactivities of human virus-specific CD8 T cells. CMV B35/IPS CD8 T cells cross-reacted with HLA-B51 and/or HLA-B58/B57 (23% of tetramer-positive individuals), FLU A2/GIL (influenza IMP[58-66] HLA-A*02:01/GILGFVFTL) CD8 T cells with HLA-B38 (90% of tetramer-positive individuals), and VZV A2/ALW (varicella zoster virus IE62[593-601] HLA-A*02:01/ALWALPHAA) CD8 T cells with HLA-B55 (two unrelated individuals). Cross-reactivity was tested against different cell types including endothelial and epithelial cells. All cross-reactive T cells expressed a memory phenotype, emphasizing the importance for transplantation. We conclude that public allo-HLA cross-reactivity of virus-specific memory T cells is not uncommon and may create novel opportunities for alloreactivity prediction and risk estimation in transplantation.

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Section: Methodsmentioning

confidence: 99%

“…Cytotoxicity was determined by 51 chromium ( 51 Cr)‐release assay, as previously described . In short, CD8 + T cell clones were stimulated with 51 Cr‐labeled PHA blasts, EBV‐LCLs, PTECs, and HUVECs for 4 h at 37°C in IMDM (Lonza) supplemented with penicillin/streptavidin, glutamine, 5% FCS (Lonza), 5% HS, and IL‐2 (10 U/mL).…”

Section: Methodsmentioning

confidence: 99%

Allo-HLA Cross-Reactivities of Cytomegalovirus-, Influenza-, and Varicella Zoster Virus–Specific Memory T Cells Are Shared by Different Healthy Individuals

Heuvel

Heutinck

Meer-Prins

et al. 2017

American Journal of Transplantation

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“…The aim of the current study was to evaluate the safety and potential efficacy of infusing low doses of donor T-cells, depleted of CD45RA+ naïve T lymphocytes. Although the potential for alloreactivity in the memory T-cell fraction was shown to be significantly reduced by several studies [15,17], cross-reactivity of the memory T-cell repertoire with allogeneic HLA is a known phenomenon [20][21][22][23]. The true potential of memory T lymphocytes to induce GVHD in a particular clinical setting is unknown thus far.…”

Section: Discussionmentioning

confidence: 99%

Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: results of a pilot trial

Maschan

Blagov

Shelikhova

et al. 2017

Bone Marrow Transplant

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Recovery of immunity is delayed in recipients of T-depleted grafts. Adoptive transfer of memory T-cells may improve immune response to common pathogens. A cohort of 53 patients with malignant (n = 36) and non-malignant conditions (n = 17) received TCR alpha/beta depleted grafts from haploidentical (n = 25) or MUD (n = 28) donors. Donor lymphocytes were depleted of CD45RA-positive cells. At a median of 48 days after transplantation, patients received DLI at 25 × 10/kg CD3 cells from haploidentical or 100 × 10/kg CD3 from MUD donors. Up to 3 doses of donor lymphocytes were administered at monthly intervals, escalating to 100 × 10/kg in haploidentical transplants and 300 × 10/kg in MUD transplants. At a median follow-up of 23 months, the cumulative incidence of de novo acute GVHD after DLI is 2% (1 of 43), while the rate of reactivation of preexisting aGVHD was 50% (5 of 10). The transplant-related mortality is 6%. The overall survival rates are 80% and 88% in malignant and non-malignant conditions, respectively. Among patients with absent CMV-specific immune reactivity at baseline (n = 31) expansion of CMV-specific T-cells was demonstrated in 20 (64.5%) within 100 days. Infusions of low dose donor memory T-lymphocytes are safe and constitute a simple measure to prevent infections in the setting of alpha/beta T cell-depleted transplantation.

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“…Peptides for CMV: HLA-A * 02:01-restricted pp65-derived NLVPMVATV (A2 NLV ) epitope, EBV: HLA-B * 07:02-restricted EBNA-3A-derived RPPIFIRRL (B7 RPP ) epitope and IAV: HLA-A * 02:01-restricted matrix protein-derived GILGFVFTL (A2 GIL ) epitope. Virusspecific CD8 + T cell clones from chronically-infected individuals were generated following single-cell sorting based on tetramer staining using the HLA-B * 57:01-restricted TSTLQEQIGW (B57 TW10 ) epitope derived from HIV-1 Gag protein for A16 and 457 (20) or EBV: B7 RPP epitope for HD9G6 (21), as previously described (2,22,23).…”

Section: Virus-specific Cd8 + T Cell Lines or Clonesmentioning

confidence: 99%

Preferential HLA-B27 Allorecognition Displayed by Multiple Cross-Reactive Antiviral CD8+ T Cell Receptors

et al. 2020

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T cells provide essential immunosurveillance to combat and eliminate infection from pathogens, yet these cells can also induce unwanted immune responses via T cell receptor (TCR) cross-reactivity, also known as heterologous immunity. Indeed, pathogen-induced TCR cross-reactivity has shown to be a common, robust, and functionally potent mechanism that can trigger a spectrum of human immunopathologies associated with either transplant rejection, drug allergy, and autoimmunity. Here, we report that several virus-specific CD8 + T cells directed against peptides derived from chronic viruses (EBV, CMV, and HIV-1) presented by high frequency HLA-A and -B allomorphs differentially cross-react toward HLA-B27 allotypes in a highly focused and hierarchical manner. Given the commonality of cross-reactive T cells and their potential contribution to adverse outcomes in allogeneic transplants, our study demonstrates that multiple antiviral T cells recognizing the same HLA allomorph could pose an extra layer of complexity for organ matching.

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Detection of Allo-HLA Cross-Reactivity by Virus-specific Memory T-Cell Clones Using Single HLA-Transfected K562 Cells

Cited by 15 publications

References 4 publications

Allo-HLA Cross-Reactivities of Cytomegalovirus-, Influenza-, and Varicella Zoster Virus–Specific Memory T Cells Are Shared by Different Healthy Individuals

Allo-HLA Cross-Reactivities of Cytomegalovirus-, Influenza-, and Varicella Zoster Virus–Specific Memory T Cells Are Shared by Different Healthy Individuals

Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: results of a pilot trial

Preferential HLA-B27 Allorecognition Displayed by Multiple Cross-Reactive Antiviral CD8+ T Cell Receptors

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