Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain.
J Vis Exp
; (116)2016 10 25.
Article
en En
| MEDLINE
| ID: mdl-27805596
ABSTRACT
T cell receptors (TCRs) are used clinically to direct the specificity of T cells to target tumors as a promising modality of immunotherapy. Therefore, cloning TCRs specific for various tumor-associated antigens has been the goal of many studies. To elicit an effective T cell response, the TCR must recognize the target antigen with optimal affinity. However, cloning such TCRs has been a challenge and many available TCRs possess sub-optimal affinity for the cognate antigen. In this protocol, we describe a method of cloning de novo high affinity antigen-specific TCRs using existing TCRs by exploiting hemichain centricity. It is known that for some TCRs, each TCRα or TCRß hemichain do not contribute equally to antigen recognition, and the dominant hemichain is referred to as the centric hemichain. We have shown that by pairing the centric hemichain with counter-chains differing from the original counter-chain, we are able to maintain the antigen specificity, while modulating its interaction strength for the cognate antigen. Thus, the therapeutic potential of a given TCR can be improved by optimizing the pairing between the centric and counter hemichains.
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Bases de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos T
Tipo de estudio:
Guideline
Límite:
Humans
Idioma:
En
Revista:
J Vis Exp
Año:
2016
Tipo del documento:
Article