Priming of Allo-HLA-DP-Specific Reactivity from the Naïve T Cell Compartment Is Not Exclusively Mediated by Professional Antigen-Presenting Cells

Laghmouchi, Aicha; Hoogstraten, Conny; Falkenburg, J.H. Frederik; Jedema, Inge

doi:10.1016/j.bbmt.2020.03.001

Cited by 1 publication

(8 citation statements)

References 47 publications

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“…HLA-DP typing of the responder and stimulator combinations is shown in Supplementary Table 2. Large numbers of allo-HLA-DPreactive T-cell clones (170 from response 1 and 440 from response 2) were identified previously (39). In-depth analyses of allo-HLA-DP-directed cross-reactivity using the panel of HLA-DP-transduced K562 cell lines was performed with a selected number of allo-HLA-DP reactive T-cell clones (16 from response 1 and 19 from response 2) with consistent reactivity and sufficient proliferative capacity.…”

Section: Allo-hla-dp-reactive T Cells Can Show Cross-reactivity Again...mentioning

confidence: 85%

“…Unmanipulated peripheral blood (without previous granulocyte colony-stimulating factor stimulation) was obtained from healthy donors after informed consent. Responder CD4 T cells were isolated by magnetic activated cell sorting (MACS) from peripheral blood mononuclear cells (PBMC) as previously described ( 39 ). The CD4 T cells were stimulated with irradiated (25 Gy) HLA-DP-mismatched antigen-presenting cells (APC) in a 10 to 1 responder to stimulator cell ratio in two different in vitro T-cell responses targeting HLA-DPB1*01:01 and HLA-DPB1*03:01 or HLA-DPB1*03:01 and HLA-DPB1*04:01, respectively (HLA-DP typing of the responder and stimulator combinations is shown in Supplementary Table 2 ), as described previously ( 39 ).…”

Section: Methodsmentioning

confidence: 99%

“…Responder CD4 T cells were isolated by magnetic activated cell sorting (MACS) from peripheral blood mononuclear cells (PBMC) as previously described ( 39 ). The CD4 T cells were stimulated with irradiated (25 Gy) HLA-DP-mismatched antigen-presenting cells (APC) in a 10 to 1 responder to stimulator cell ratio in two different in vitro T-cell responses targeting HLA-DPB1*01:01 and HLA-DPB1*03:01 or HLA-DPB1*03:01 and HLA-DPB1*04:01, respectively (HLA-DP typing of the responder and stimulator combinations is shown in Supplementary Table 2 ), as described previously ( 39 ). The cells were cultured in IMDM containing 10% heat-inactivated human serum (ABOS; Sanquin) supplemented with IL-7 (10 ng/ml, Miltenyi Biotec), IL-15 (0.1 ng/ml, Miltenyi Biotec) and IL-2 (50 IU/ml, Novartis Sandoz).…”

Section: Methodsmentioning

confidence: 99%

Section: The Generation Of Allo-hla-dp-restricted Cd4 T-cell Clonesmentioning

confidence: 99%

“…Responder CD4 T cells were isolated by magnetic activated cell sorting (MACS) from peripheral blood mononuclear cells (PBMC) as previously described (39). The CD4 T cells were stimulated with irradiated ( 25 2), as described previously (39). The cells were cultured in IMDM containing 10% heat-inactivated human serum (ABOS; Sanquin) supplemented with IL-7 (10 ng/ ml, Miltenyi Biotec), IL-15 (0.1 ng/ml, Miltenyi Biotec) and IL-2 (50 IU/ml, Novartis Sandoz).…”

Section: The Generation Of Allo-hla-dp-restricted Cd4 T-cell Clonesmentioning

confidence: 99%

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Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity

et al. 2022

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In the context of HLA-DP-mismatched allogeneic stem cell transplantation, mismatched HLA-DP alleles can provoke profound allo-HLA-DP-specific immune responses from the donor T-cell repertoire leading to graft-versus-leukemia effect and/or graft-versus-host disease in the patient. The magnitude of allo-HLA-DP-specific immune responses has been shown to depend on the specific HLA-DP disparity between donor and patient and the immunogenicity of the mismatched HLA-DP allele(s). HLA-DP peptidome clustering (DPC) was developed to classify the HLA-DP molecules based on similarities and differences in their peptide-binding motifs. To investigate a possible categorization of HLA-DP molecules based on overlap of presented peptides, we identified and compared the peptidomes of the thirteen most frequently expressed HLA-DP molecules. Our categorization based on shared peptides was in line with the DPC classification. We found that the HLA-DP molecules within the previously defined groups DPC-1 or DPC-3 shared the largest numbers of presented peptides. However, the HLA-DP molecules in DPC-2 segregated into two subgroups based on the overlap in presented peptides. Besides overlap in presented peptides within the DPC groups, a substantial number of peptides was also found to be shared between HLA-DP molecules from different DPC groups, especially for groups DPC-1 and -2. The functional relevance of these findings was illustrated by demonstration of cross-reactivity of allo-HLA-DP-reactive T-cell clones not only against HLA-DP molecules within one DPC group, but also across different DPC groups. The promiscuity of peptides presented in various HLA-DP molecules and the cross-reactivity against different HLA-DP molecules demonstrate that these molecules cannot be strictly categorized in immunogenicity groups.

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Section: Allo-hla-dp-reactive T Cells Can Show Cross-reactivity Again...mentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: The Generation Of Allo-hla-dp-restricted Cd4 T-cell Clonesmentioning

confidence: 99%

“…Responder CD4 T cells were isolated by magnetic activated cell sorting (MACS) from peripheral blood mononuclear cells (PBMC) as previously described (39). The CD4 T cells were stimulated with irradiated ( 25 2), as described previously (39). The cells were cultured in IMDM containing 10% heat-inactivated human serum (ABOS; Sanquin) supplemented with IL-7 (10 ng/ ml, Miltenyi Biotec), IL-15 (0.1 ng/ml, Miltenyi Biotec) and IL-2 (50 IU/ml, Novartis Sandoz).…”

Section: The Generation Of Allo-hla-dp-restricted Cd4 T-cell Clonesmentioning

confidence: 99%

See 3 more Smart Citations

Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity

et al. 2022

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View full text Add to dashboard Cite

show abstract

Priming of Allo-HLA-DP-Specific Reactivity from the Naïve T Cell Compartment Is Not Exclusively Mediated by Professional Antigen-Presenting Cells

Cited by 1 publication

References 47 publications

Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity

Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity

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