Magnitude of Off-Target Allo-HLA Reactivity by Third-Party Donor-Derived Virus-Specific T Cells Is Dictated by HLA-Restriction.

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 cel

SUBMITTER: Huisman W 

PROVIDER: S-EPMC8039299 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature