Motozono, Chihiro, Bridgeman, John S., Price, David  ORCID: https://orcid.org/0000-0001-9416-2737, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135 and Ueno, T.
2015.
Clonotypically similar hybrid ab T cell receptors can exhibit markedly
different surface expression, antigen specificity and cross-reactivity.
Clinical and Experimental Immunology
180
(3)
, pp. 560-570.
10.1111/cei.12610
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Abstract
Emerging data indicate that particular major histocompatibility complex (MHC)-bound antigenic peptides can be recognized by identical or nearidentical ab T cell receptors (TCRs) in different individuals. To establish the functional relevance of this phenomenon, we artificially paired a and b chains from closely related TCRs specific for the human leucocyte antigen (HLA)-B*35:01-restricted HIV-1 negative regulatory factor (Nef)- derived epitope VY8 (VPLRPMTY, residues 74–81). Several hybrid TCRs generated in this manner failed to express at the cell surface, despite near homology with naturally isolated ab chain combinations. Moreover, a substantial proportion of those ab TCRs that did express lost specificity for the index VY8 peptide sequence. One such hybrid ab pair gained neo-variant specificity in the context of the VY8 backbone. Collectively, these data show that clonotypically similar TCRs can display profound differences in surface expression, antigen specificity and cross-reactivity with potential relevance for the control of mutable viruses.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | R Medicine > R Medicine (General) |
| Additional Information: | Article first published online 15 May 2015 |
| Publisher: | Wiley-Blackwell |
| ISSN: | 0009-9104 |
| Funders: | Wellcome Trust |
| Date of First Compliant Deposit: | 30 March 2016 |
| Date of Acceptance: | 19 February 2015 |
| Last Modified: | 04 May 2023 23:15 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/74260 |
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