biostudies-literatureStief TANCI NIH HHS198-208https://www.ebi.ac.uk/biostudies/studies/S-EPMC8753271biostudies-literatureUnknown30(1)Viral infections cause life-threatening disease in immunocompromised patients and especially following transplantation. T cell receptor (TCR) engineering redirects specificity and can bring significant progress to emerging adoptive T cell transfer (ACT) approaches. T cell epitopes are well described, although knowledge is limited on which TCRs mediate protective immunity. In this study, refractory adenovirus (AdV) infection after hematopoietic stem cell transplantation (HSCT) was treated with ACT of highly purified Hexon5-specific T cells using peptide major histocompatibility complex (pMHC)-Streptamers against the immunodominant human leukocyte antigen (HLA)-A∗0101-restricted peptide LTDLGQNLLY. AdV was successfully controlled through this oligoclonal ACT. Novel protective TCRs were isolaMolecular therapy : the journal of the American Society of Gene TherapyProtective T cell receptor identification for orthotopic reprogramming of immunity in refractory virus infections.PMC8753271P30 CA008748Feuchtinger TLang PMuller TRSchober KDoring MJablonowski LMKaeuferle TFeucht JBlaeschke FDennehy KMWillier SHandgretinger RBusch DHStief TAfalseProtective T cell receptor identification for orthotopic reprogramming of immunity in refractory virus infections.Viral infections cause life-threatening disease in immunocompromised patients and especially following transplantation. T cell receptor (TCR) engineering redirects specificity and can bring significant progress to emerging adoptive T cell transfer (ACT) approaches. T cell epitopes are well described, although knowledge is limited on which TCRs mediate protective immunity. In this study, refractory adenovirus (AdV) infection after hematopoietic stem cell transplantation (HSCT) was treated with ACT of highly purified Hexon5-specific T cells using peptide major histocompatibility complex (pMHC)-Streptamers against the immunodominant human leukocyte antigen (HLA)-A∗0101-restricted peptide LTDLGQNLLY. AdV was successfully controlled through this oligoclonal ACT. Novel protective TCRs were isola2022-01-01T00:00:00Z2022 Jan2025-04-04T10:59:10.775Z2025-04-04T10:59:10.775ZS-EPMC87532713405838610.1016/j.ymthe.2021.05.021