title: Human T cells expressing two additional receptors (TETARs) specific for HIV-1 recognize both epitopes.
abstract: Adoptive TCR transfer against rapidly mutating targets, such as HIV-1 or cancer, must counteract corresponding immune escape. Hence, we generated T cells expressing two additional receptors (TETARs) specific for HIV-1 by TCR mRNA electroporation. An HLA-A2-restricted gag-specific TCR and an HLA-B13-restricted nef-specific TCR were chosen. When both TCRs were transfected simultaneously, strong competitive effects occurred that were overcome by replacing the human constant domains of one TCR with murine counterparts and adapting the amounts of TCR-RNA used for transfection. The resulting TETAR responded to both epitopes with cytokine secretion and cytotoxic function. Cell sorting revealed that one individual cell indeed recognized both epitopes. The T cells diminished their reactivity to each epitope after stimulation but sequentially killed targets that presented the gag epitope and then targets that presented the nef epitope, or vice versa. Taken together, TETARs represent a sophisticated tool to study TCR functionality and might be a useful strategy in immunotherapy.
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hofmann
authors.forename: Sandra
authors.initials: S
authors.lastname: Höfflin
authors.forename: Angela
authors.initials: A
authors.lastname: Hückelhoven
authors.forename: Silke
authors.initials: S
authors.lastname: Bergmann
authors.forename: Ellen
authors.initials: E
authors.lastname: Harrer
authors.forename: Gerold
authors.initials: G
authors.lastname: Schuler
authors.forename: Jan
authors.initials: J
authors.lastname: Dörrie
authors.forename: Niels
authors.initials: N
authors.lastname: Schaft
authors.forename: Thomas
authors.initials: T
authors.lastname: Harrer
mesh_terms: D019264:Adoptive Transfer; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D018274:Electroporation; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D015488:HIV Antigens / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015728:Receptors, HIV; D054301:gag Gene Products, Human Immunodeficiency Virus