scholarly journals Prospective Tracking of Donor-Reactive T-Cell Clones in the Circulation and Rejecting Human Kidney Allografts

2021 ◽  
Vol 12 ◽  
Author(s):  
Constantin Aschauer ◽  
Kira Jelencsics ◽  
Karin Hu ◽  
Andreas Heinzel ◽  
Mariella Gloria Gregorich ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Network Analysis ◽  
Mononuclear Cells ◽  
Control Group ◽  
T Cell Clones ◽  
Cdr3 Region ◽  
Cell Clones ◽  
Protocol Biopsies ◽  
Tcr Repertoire

BackgroundAntigen recognition of allo-peptides and HLA molecules leads to the activation of donor-reactive T-cells following transplantation, potentially causing T-cell-mediated rejection (TCMR). Sequencing of the T-cell receptor (TCR) repertoire can be used to track the donor-reactive repertoire in blood and tissue of patients after kidney transplantation.Methods/DesignIn this prospective cohort study, 117 non-sensitized kidney transplant recipients with anti-CD25 induction were included. Peripheral mononuclear cells (PBMCs) were sampled pre-transplant and at the time of protocol or indication biopsies together with graft tissue. Next-generation sequencing (NGS) of the CDR3 region of the TCRbeta chain was performed after donor stimulation in mixed lymphocyte reactions to define the donor-reactive TCR repertoire. Blood and tissue of six patients experiencing a TCMR and six patients without rejection on protocol biopsies were interrogated for these TCRs. To elucidate common features of T-cell clonotypes, a network analysis of the TCR repertoires was performed.ResultsAfter transplantation, the frequency of circulating donor-reactive CD4 T-cells increased significantly from 0.86 ± 0.40% to 2.06 ± 0.40% of all CD4 cells (p < 0.001, mean dif.: -1.197, CI: -1.802, -0.593). The number of circulating donor-reactive CD4 clonotypes increased from 0.72 ± 0.33% to 1.89 ± 0.33% (p < 0.001, mean dif.: -1.168, CI: -1.724, -0.612). No difference in the percentage of donor-reactive T-cells in the circulation at transplant biopsy was found between subjects experiencing a TCMR and the control group [p = 0.64 (CD4+), p = 0.52 (CD8+)]. Graft-infiltrating T-cells showed an up to six-fold increase of donor-reactive T-cell clonotypes compared to the blood at the same time (3.7 vs. 0.6% and 2.4 vs. 1.5%), but the infiltrating TCR repertoire was not reflected by the composition of the circulating TCR repertoire despite some overlap. Network analysis showed a distinct segregation of the donor-reactive repertoire with higher modularity than the overall TCR repertoire in the blood. These findings indicate an unchoreographed process of diverse T-cell clones directed against numerous non-self antigens found in the allograft.ConclusionDonor-reactive T-cells are enriched in the kidney allograft during a TCMR episode, and dominant tissue clones are also found in the blood.Trial RegistrationClinicaltrials.gov: NCT: 03422224 (https://clinicaltrials.gov/ct2/show/NCT03422224).

T Cell Repertoire after Alpha/Beta-T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4582-4582
Author(s):  
Ivan Zvyagin ◽  
Olga Tatarinova ◽  
Ilgar Mamedov ◽  
Ekaterina Komech ◽  
Alexey Maschan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
T Cell Clones ◽  
Cell Clones ◽  
Tcr Repertoire ◽  
Repertoire Sequencing ◽  
Alpha Beta

Abstract Allogeneic transplantation of hematopoietic cells (HSCT) is an established method to treat different hematologic malignancies and disorders of hematopoietic and lymphoid system. Graft-versus-host-disease is one of the main risk factor for success of the procedure. Simultaneous depletion of alpha-beta T-cells and CD19+ cells in graft is the promising way to reduce the risk. The approach was recently introduced in clinical practice and many aspects of immune system reconstitution are still unknown. We applied improved technology for T cell receptor (TCR) repertoire sequencing to study origin and dynamics of T cell clones during 1 year follow-up period after allogeneic TCRαβ/CD19-depleted HSCT in children. We performed TCR repertoire sequencing for peripheral blood samples of patients before HSCT, at 2, 6 and 12 months after HSCT (n=21, 21, 17, 16 respectively), and for respective donor blood apheresis samples before abT/CD19 depletion. Twelve of the patients were diagnosed with acute leukemia and the others with non-malignant inherited and acquired blood disorders. For each patient data on recipient's T cell chimerism and counts of CD3+, naïve CD3+, alpha-beta T-cells and recent thymic emigrants (RTE) have been collected during 1 year follow-up period. Barcoding of each original TCR mRNA molecule passed to massive parallel sequencing allowed us to: (1) reduce sample preparation biases and quantitatively reconstruct of TCR repertoires; (2) equalize repertoire data analysis depth which is absolutely necessary for correct comparison of samples; (3) prevent risk of cross-contamination between samples and increase confidence of T clone origin determination. Two months after TCRαβ/CD19-depleted HSCT T cell repertoire mostly consists of several hundreds highly abundant clones. For patients with low recipient T cell chimerism from 13 to 504 largest T-cell clones (median 255, IQR 219, n=9, T cell chimerism <=20%) represented 80% of all T cells in peripheral blood. For comparison in healthy age-matched donors we found from 32,000 to 47,000 largest T-cell clones in identical analysis (median 43191, IQR 6493, n=14, data from Britanova O.V. et.al., JI 2014). The overall diversity at d60 after HSCT was also much less compared with the healthy subjects. We also found that most expanded T cell clones at d60 do not represent just a replica of the most expanded clones in graft samples, originating from low-abundant graft T cell clones. The diversity of T repertoire early after HSCT positively correlated with recipient T cell chimerism (the diversity was higher for those patients with higher percentage of recipient's T cells). Also patients with low chimerism had higher number of T clones originating from the graft than from d0 pre-transplant recipient repertoire in contrast to the patients with high T cell chimerism who had inverse ratio (median number of patient's clonotypes shared between graft and d0 was 56 or 3 for patients with low or absent chimerism (IQR = 24 or 19.25, n = 5) and 21.5 or 321.5 for patients with T cell chimerism >2% (IQR = 46.5 or 724.75, n = 10)). In addition CD4+ RTE count was higher for patients with high T cell chimerism. This observation was additionally confirmed by analysis of flow cytometry data for the expanded cohort of 105 patients at d60 after αβT-cell depleted HSCT (Wilcoxon rank sum test p-value = 0.002). Our results demonstrate that early after αβT-cell depleted HSCT repertoire of T cells are extremely skewed and unlikely able protect recipient efficiently. Observed recovery of T cell count mostly results from expansion of a few clones that have to divide intensely for the whole 60 days period in order to achieve the observed counts. Early reconstitution of TCR diversity and RTE counts in patients with substantial recipient T cell chimerism is mostly explained by surviving recipient T cells and intrathymic T cell progenitors, respectively. This work was supported by the Russian Science Foundation project №14-35-00105. Zvyagin I. is supported by grant MK-4583.2015.4. Disclosures No relevant conflicts of interest to declare.

scholarly journals Characterization of Human CD4+ T-Cell Clones Recognizing Conserved and Variable Epitopes of the Lassa Virus Nucleoprotein

2000 ◽  
Vol 74 (5) ◽  
pp. 2186-2192 ◽  
Author(s):  
Jan ter Meulen ◽  
Marlis Badusche ◽  
Kristiane Kuhnt ◽  
Andrea Doetze ◽  
Judith Satoguina ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Amino Acid Sequences ◽  
Eastern Africa ◽  
Proliferation Index ◽  
Lassa Virus ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones

ABSTRACT T cells must play the major role in controlling acute human Lassa virus infection, because patients recover from acute Lassa fever in the absence of a measurable neutralizing antibody response. T cells alone seem to protect animals from a lethal Lassa virus challenge, because after experimental vaccination no neutralizing antibodies are detectable. In order to study human T-cell reactivity to single Lassa virus proteins, the nucleoprotein (NP) of Lassa virus, strain Josiah, was cloned, expressed in Escherichia coli, and affinity purified. Peripheral blood mononuclear cells (PBMC) obtained from 8 of 13 healthy, Lassa virus antibody-positive individuals living in the Republic of Guinea, western Africa, were found to proliferate in response to the recombinant protein (proliferation index ≥10). PBMC obtained from one individual with a particularly high proliferative response were used to generate 50 NP-specific T-cell clones (TCC). For six of these the epitopes were mapped with overlapping synthetic peptides derived from the sequence of the NP. These CD4+TCC displayed high specific proliferation and produced mainly gamma interferon upon stimulation with NP. Because variation of up to 15% in the amino acid sequences of the structural proteins of naturally occurring Lassa virus variants has been observed, the reactivity of the TCC with peptides derived from the homologous epitopes of the Nigeria strain of Lassa virus and of the eastern Africa arenavirus Mopeia was tested. With the Nigeria strain of Lassa virus the levels of homology were 100% for two of these epitopes and 85% for three of them, whereas homology with the respective Mopeia epitopes ranged from 92 to 69%. Reactivity of the TCC with peptides derived from the variable epitopes of the Nigeria strain and of Mopeia was reduced or completely abolished. This report shows for the first time that seropositive individuals from areas of endemicity have very strong memory CD4+ T-cell responses against the NP of Lassa virus, which are partly strain specific and partly cross-reactive with other Lassa virus strains. Our findings may have important implications for the strategy of designing recombinant vaccines against this mainly T-cell-controlled human arenavirus infection.

Molecular Identification of Individual T Cell Clones Specific for Graft- Versus-Leukemia Reaction

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1249-1249
Author(s):  
Veronika Foltankova ◽  
Eva Matejkova ◽  
Milan Bartos ◽  
Milos Dendis ◽  
Dana Novotna ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Clone ◽  
Cell Receptor ◽  
Unique Sequence ◽  
Hematopoietic Stem ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Clone

Abstract Graft-verus-leukemia (GVL) effect in hematopoietic stem cell transplantation (HSCT) is usually complicated by the alloreactivity of donor T cells which leads to acute graft-versus-host (GVH) disease. GVL and GVH reactions are proved to be mediated by different T cell clones. The objective of this study was to identify and characterize T cells clones with specific antileukemia activity without mediating GVHD. We have performed primary mixed leukocyte reaction (MLR) using patient non-leukemic irradiated peripherial blood mononuclear cells (PBMC) as stimulators and donor PBMC as responders. To prepare GVL specific T cells, activated alloreactive T cells were first selectively depleted with an anti-CD25 immunotoxin (Michalek, et al. PNAS2003, 100: 1180–4). Allodepleted T cells were then stimulated in secondary MLR using irradiated leukemia cells from the same patient. Activated leukemia-reactive cells were purified by immunomagnetic selection or by FACS based on INF-γ or CD25 expression, respectively. Clonotypic assay was used for identification of individual leukemia-specific T cell clones (Michalek, et al. Lancet2003, 361: 1183–5; Michalek, et al. J Immunol2007, 178: 6789– 5). This highly sensitive assay is based on detailed analysis of T cell receptor β VDJ unique sequence (TCRB-VDJ). mRNA was extracted from sortred activated cells and cDNA synthetized by anchored reverse transcription. Target TCRB-VDJ gene sequence was amplified by anchor PCR and used to transform bacteria. Bacterial colonies were picked for plasmid isolation and subsequent direct automated sequencing of the TCRBVDJ sequences. We assume that the frequency of particular TCRB-VDJ sequences among bacterial clones after transformation are proportional to the frequency of those sequences in the original population of T cells activated by GVH or GVL reaction. We investigated the presence of individual antileukemic T cell clones in patients with acute myeloid leukemia (AML) and chronic lymphatic leukemia (CLL), and defined them by the TCRB-VDJ unique sequence. The sequences that occured in more than 10% bacterial colonies are likely to represent the most immunodominant clones. Populations of antileukemic T cell clones were oligoclonal, i.e. we observed limited number of individual immunodominat clones which plays important role in GVL reaction. In first CLL patient who had undergone HSCT, six antileukemic T cell clones were identified, four of them are considered to be immunodominant. In second CLL patient after HSCT, only one highly immunodominat autileukemic T cell clone was observed. This specific clone was further monitored by quantitative real-time PCR in patients peripherial blood.

T-cell responses associated with neonatal alloimmune thrombocytopenia: isolation of HPA-1a–specific, HLA-DRB3*0101–restricted CD4+ T cells

Blood ◽  
2009 ◽  
Vol 113 (16) ◽  
pp. 3838-3844 ◽  
Author(s):  
Maria Therese Ahlen ◽  
Anne Husebekk ◽  
Mette Kjær Killie ◽  
Bjørn Skogen ◽  
Tor B. Stuge
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
T Cell Responses ◽  
Antigen Specificity ◽  
Proliferating Cells ◽  
T Cell Clones ◽  
Cell Responses ◽  
Cell Clones ◽  
Alloimmune Thrombocytopenia

Abstract T-cell responses have been implicated in the development of HPA-1a–induced neonatal alloimmune thrombocytopenia (NAIT). However, HPA-1a–specific T cells have neither been isolated nor characterized. Here, we aimed to determine whether HPA-1a–specific T cells could be isolated from HPA-1a–immunized women. In the present study, peripheral blood mononuclear cells (PBMCs) from an HPA-1a–alloimmunized woman were cultured for weeks in the presence of HPA-1a peptide, labeled with CFSE, and assayed for antigen-specific proliferation. Individual proliferating cells were isolated by fluorescence-activated cell sorting and expanded in culture. Antigen specificity and HLA restriction were determined by cytokine secretion (enzyme-linked immunospot [ELISPOT]) and proliferation assays. Several CD3+CD4+ T-cell clones were isolated that proliferated and secreted cytokines in response to HPA-1a peptide. Two of these clones have been established in long-term culture in our laboratory. Both of these recognize synthetic as well as naturally processed HPA-1a antigen, and the recognition is restricted by the MHC molecule HLA-DRB3*0101 that is strongly associated with NAIT. These HPA-1a–specific T-cell clones represent unambiguous evidence for the association of T-cell responses with NAIT, and they will serve as unique tools to elucidate the cellular immune response that may result in NAIT.

scholarly journals THU0046 A PIPELINE TO STUDY ANTIGEN-SPECIFIC CD4+ T CELLS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 235.1-236
Author(s):  
R. Kumar ◽  
N. Yoosuf ◽  
C. Gerstner ◽  
S. Turcinov ◽  
K. Chemin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Tenascin C ◽  
Tetramer Staining ◽  
Tcr Repertoire ◽  
Citrullinated Antigen

Background:Autoimmunity to citrullinated autoantigens forms a critical component of disease pathogenesis in rheumatoid arthritis (RA). Presence of anti-citrullinated protein antibodies (ACPAs) in patients has high diagnostic value. Recently, several citrullinated antigen specific CD4+T cells have been described. However, detailed studies of their T-cell receptor usage and in-vivo profile suffer from the disadvantage that these cells are present at very low frequencies. In this context, we here present a pipeline for TCR repertoire analysis of antigen-specific CD4+T cells from RA patients, including both citrulline and influenza (control) specificities using in-vitro peptide challenge induced-cell expansion.Objectives:To enable studies of the T cell repertoire of citrullinated antigen-specific CD4+T cells in rheumatoid arthritisMethods:Peripheral blood mononuclear cells (PBMCs) (n=7) and synovial fluid mononuclear cells (SFMCs) (n=5) from HLA-DR*0401-postive RA patients were cultured in the presence of citrullinated Tenascin C peptide cocktails or influenza peptides (positive control). Citrulline reactive cells were further supplemented with recombinant human IL-15 and IL-7 on day 2. All cultures were replenished with fresh medium on day 6 and rIL-2 was added every 2 days from then. Assessment of proportion of peptide-HLA-tetramer positive cells was performed using flow cytometry whereby individual antigen-specific CD4+T cells were sorted into 96-well plates containing cell lysis buffer, followed by PCR-based alpha/beta TCR sequencing. TCR sequencing data was demultiplexed and aligned for TCR gene usage using MiXCR. Some tetramer positive cells were sorted into complete medium containing human IL-2 and PHA for expansion of antigen-specific cells. Cells were supplemented with irradiated allogenic PBMCs (30 times number of antigen specific cells). Clones of antigen specific CD4+T cells were further subjected to tetramer staining to confirm expansion of cells.Results:As evidenced by increase in frequency of tetramer positive CD4+T cells, in vitro peptide stimulation resulted in expansion of both influenza specific (Fig. 1a) and citrullinated antigen specific (Fig. 1b) CD4+T cells. Polyclonal in-vitro expansion of tenascin C tetramer positive sorted cells followed by tetramer staining further confirmed antigen specificity and enrichment for antigen specific CD4+T cells after polyclonal stimulation (Fig.1c). TCR repertoire analysis in PB and SF dataset from the first patient showed clonal expansion of influenza specific cells in both sites. Synovial fluid had more diversity of expanding clones as compared to paired PB, with few expanded clones being shared among SF and PB. We observed a more diverse TCR repertoire in citrulline specific CD4+T cells. We also observed sharing of TCR alpha chains among different citrulline specific CD4+T cell clones.Fig. 1In-vitroexpansion of antigen specific CD4+T cells:Conclusion:This method provides a highly suitable approach for investigating TCR specificities of antigen specific CD4+T cells under conditions of low cell yields. Building on this dataset will allow us to assess specific features of TCR usage of autoreactive T cells in RA.PBMCs were cultured in presence of (a) influenza (HA, MP54) and (b) citrullinated tenascin peptides. The proportion of antigen specific CD4+T cells was assessed using HLA-class II tetramer staining. We observed an increase in frequency of (a) Infleunza specific cells (red dots in upper left and lower right quadrants) and (b) citrullinated tenascin C specific cells (red dots in lower right quadrant), at day 13 post culture as compared to day 3. (c) Sorting of citrullinated tenascin specific CD4+T cells, followed by PHA expansion resulted in visible increase in proportion of citrullinated tenascin specific CD4+T cells.Disclosure of Interests:Ravi kumar: None declared, Niyaz Yoosuf: None declared, Christina Gerstner: None declared, Sara Turcinov: None declared, Karine Chemin: None declared, Vivianne Malmström Grant/research support from: VM has had research grants from Janssen Pharmaceutica

Cord blood mononuclear cells and milk-specific T-cell clones are tools to evaluate the residual immunogenicity of hydrolyzed milk formulas

1998 ◽  
Vol 101 (4) ◽  
pp. 514-520 ◽  
Author(s):  
Zsolt Szépfalusi ◽  
Ivo Nentwich ◽  
Eva Josta ◽  
Marianne Gerstmayra ◽  
Christof Ebner ◽  
...  
Keyword(s):  
T Cell ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
T Cell Clones ◽  
Cell Clones ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

scholarly journals Macrophage colony-stimulating factor (CSF-1) gene expression in human T- lymphocyte clones

Blood ◽  
1991 ◽  
Vol 77 (4) ◽  
pp. 780-786 ◽  
Author(s):  
MM Hallet ◽  
V Praloran ◽  
H Vie ◽  
MA Peyrat ◽  
G Wong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Phenotypic Diversity ◽  
Calcium Ionophore ◽  
Colony Stimulating Factor ◽  
T Cell Clones ◽  
Cell Clones ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Macrophage colony stimulating factor (CSF-1) is one of several cytokines that control the differentiation, survival, and proliferation of monocytes and macrophages. A set of 11 human T-cell clones, chosen for their phenotypic diversity, were tested for their ability to express CSF-1 mRNA. After 5 hours of stimulation with phorbol myristate acetate (PMA) + calcium ionophore (Cal), all T-cell clones expressed a major 4-kb transcript, a less abundant 2-kb transcript, and several other minor species. This pattern of expression is typical for CSF-1 mRNAs. Furthermore, of the two alloreactive T-cell clones analyzed, only one showed a definitive message for CSF-1 on specific antigenic stimulation, but with delayed kinetics and less efficiency. Both conditions of stimulation induced the release of CSF-1 protein by T cells in the culture medium. Together, these findings demonstrate for the first time that normal T cells are able to produce CSF-1, previous reports being limited to two cases of tumoral cells of the T-cell lineage.

Selective Depletion of Alloreactive T Cells and Study of Anti-Tumor Activity of Specific T Cell Clones in Patients with Leukemia and Renal Carcinoma

2007 ◽  
Vol 123 ◽  
pp. S106-S107
Author(s):  
Eva Matejkova ◽  
Zuzana Hrotekova ◽  
Drahomira Kyjovska ◽  
Jaroslav Michalek ◽  
Petra Vidlakova
Keyword(s):  
T Cells ◽  
T Cell ◽  
Renal Carcinoma ◽  
T Cell Clones ◽  
Alloreactive T Cells ◽  
Cell Clones ◽  
Selective Depletion ◽  
Anti Tumor Activity

scholarly journals Evaluation of Various Strategies to Generate NPM1mut-Specific T Cell Clones

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5718-5718 ◽  
Author(s):  
Elke Ruecker-Braun ◽  
Falk Heidenreich ◽  
Cornelia S Link ◽  
Maria Schmiedgen ◽  
Rebekka Wehner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Checkpoint Inhibitors ◽  
Single Cells ◽  
Molecular Genetic ◽  
Specific Antigen ◽  
Positive Control ◽  
Low Frequencies ◽  
T Cell Clones ◽  
Cell Clones

Abstract Mutated nucleophosmin (NPM1) was identified as a promising leukemia-specific antigen for cytotoxic T lymphocytes (CTL). NPM1 is a multifunctional nucleocytoplasmic shuttling phosphoprotein. In AML patients with normal cytogenetics NPM1 mutations are the most frequent molecular genetic abnormalities, accounting for up to 60% of the patients. The peptide (AIQDLCLAV) derived from the mutated NPM1 (NPM1mut) has been described to elicit a CTL response restricted to HLA-A*02:01. We observed that NPM1mut multimer+ T cells were very rare in peripheral blood. The limitation of the multimer technology is the absence of a positive control; nevertheless it is an attractive tool to generate antigen positive T cell clones. The goal was to compare strategies for the generation of NPM1mut multimer+ T cell clones systematically. For this purpose we analyzed blood samples from two patients with AML after transplantation and six different healthy donors. We explored different strategies to isolate HLA-A*02:01 restricted NPM1mut multimer+ T single cells. The first strategy was to isolate multimer+ T cells directly from the blood without any supplements by single cell sorting. The second strategy was to sort multimer+ T cells which were previously CD8+ enriched supplementing the media either with or without IL-21. Published by Yongqing et al.IL-21 enhances the generation of human antigen-specific CD8+ T cells. A further strategy was to previously enrich CD14+ cells for the generation of autologous monocyte-derived dendritic cells (MoDCs). The co-cultivation of MoDCs loaded with the NPM1mut peptide and CD8+ cells were performed either with or without IL-21, as well. We expanded the last strategy by a second round of NPM1mut-specific stimulation. So far it was not possible to generate NPM1mut-specific T cell clones based on the advanced strategies and consistently there is no data published on NPM1mut multimer+ T cell clones. This fact raises the question why NPM1mut specific clones display such low frequencies. We want to point out that although we varied the strategies and we used eight different donors the isolation of NPM1mut-specific T cells restricted to HLA-A*02:01 apparently is challenging. Greater efforts, e.g. a larger number of donors or the use of immunological checkpoint inhibitors during cell culture are needed. Disclosures Thiede: AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.

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