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• W3149452783 abstract "T-cell products derived from third-party donors are clinically applied, but harbor the risk of off-target toxicity via induction of allo-HLA cross-reactivity directed against mismatched alleles. We used third-party donor-derived virus-specific T cells as model to investigate whether virus-specificity, HLA restriction and/or HLA background can predict the risk of allo-HLA cross-reactivity. Virus-specific CD8 pos T cells were isolated from HLA-A * 01:01/B * 08:01 or HLA-A * 02:01/B * 07:02 positive donors. Allo-HLA cross-reactivity was tested using an EBV-LCL panel covering 116 allogeneic HLA molecules and confirmed using K562 cells retrovirally transduced with single HLA-class-I alleles of interest. HLA-B * 08:01-restricted T cells showed the highest frequency and diversity of allo-HLA cross-reactivity, regardless of virus-specificity, which was skewed toward multiple recurrent allogeneic HLA-B molecules. Thymic selection for other HLA-B alleles significantly influenced the level of allo-HLA cross-reactivity mediated by HLA-B * 08:01-restricted T cells. These results suggest that the degree and specificity of allo-HLA cross-reactivity by T cells follow rules. The risk of off-target toxicity after infusion of incompletely matched third-party donor-derived virus-specific T cells may be reduced by selection of T cells with a specific HLA restriction and background." @default.
• W3149452783 created "2021-04-13" @default.
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• W3149452783 date "2021-03-29" @default.
• W3149452783 modified "2023-10-18" @default.
• W3149452783 title "Magnitude of Off-Target Allo-HLA Reactivity by Third-Party Donor-Derived Virus-Specific T Cells Is Dictated by HLA-Restriction" @default.
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• W3149452783 doi "https://doi.org/10.3389/fimmu.2021.630440" @default.
• W3149452783 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8039299" @default.
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• W3149452783 hasPublicationYear "2021" @default.
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