T cell receptor libraries
First Claim
1. A method for generating at least one receptor having a desired specificity and/or affinity for a ligand, whereby said receptor undergoes functional processing after ligand-binding, comprising constructing a sequence encoding such a receptor and allowing for the product of said sequence to be expressed in a suitable environment wherein said processing after ligand-binding can occur.
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Abstract
Strategies for TCR-display that closely mimic the in vivo situation, meaning at least a stable expression of TCRs to be displayed in mammalian cells exemplified by retroviral insertion of a T cell receptor library into a TCR-negative T cell host. Such mammalian cell line TCR libraries, especially T cell line-displayed TCR libraries would not only allow the selection of desirable TCRs by biochemical means, but also offer the possibility to directly test the functional behavior of selected TCRs. By generating a TCR library that is diversified in its CDR3beta structure, we were able to select novel TCRs that either share specificity with the parental TCR, or that have acquired a specificity for a variant T cell epitope. A change in TCR specificity can thought of as an increase in TCR affinity for the variant epitope.
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27 Claims
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1. A method for generating at least one receptor having a desired specificity and/or affinity for a ligand, whereby said receptor undergoes functional processing after ligand-binding, comprising
constructing a sequence encoding such a receptor and allowing for the product of said sequence to be expressed in a suitable environment wherein said processing after ligand-binding can occur.
Specification