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

ABSTRACT: Emerging data indicate that particular major histocompatibility complex (MHC)-bound antigenic peptides can be recognized by identical or near-identical ?? T cell receptors (TCRs) in different individuals. To establish the functional relevance of this phenomenon, we artificially paired ? and ? 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 ?? chain combinations. Moreover, a substantial proportion of those ?? TCRs that did express lost specificity for the index VY8 peptide sequence. One such hybrid ?? 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.

SUBMITTER: Motozono C 

PROVIDER: S-EPMC4449784 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature