Clonotypically similar hybrid ab T cell receptors can exhibit markedly different surface expression, antigen specificity and cross-reactivity

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:	Medicine 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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