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.
journal_name
Bloodjournal_title
Bloodauthors
Hofmann C,Höfflin S,Hückelhoven A,Bergmann S,Harrer E,Schuler G,Dörrie J,Schaft N,Harrer Tdoi
10.1182/blood-2011-04-347005subject
Has Abstractpub_date
2011-11-10 00:00:00pages
5174-7issue
19eissn
0006-4971issn
1528-0020pii
blood-2011-04-347005journal_volume
118pub_type
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