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

C. Motozono, J. S. Bridgeman, D. A. Price, A. K. Sewell, T. Ueno

Research output: Contribution to journalArticle

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Abstract

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

Original languageEnglish
Pages (from-to)560-570
Number of pages11
JournalClinical and Experimental Immunology
Volume180
Issue number3
DOIs
Publication statusPublished - Jun 1 2015

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Hybrid Cells
Surface Antigens
T-Cell Antigen Receptor
HLA Antigens
Major Histocompatibility Complex
HIV-1
Epitopes
Viruses
Peptides

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Clonotypically similar hybrid αβ T cell receptors can exhibit markedly different surface expression, antigen specificity and cross-reactivity. / Motozono, C.; Bridgeman, J. S.; Price, D. A.; Sewell, A. K.; Ueno, T.

In: Clinical and Experimental Immunology, Vol. 180, No. 3, 01.06.2015, p. 560-570.

Research output: Contribution to journalArticle

Motozono, C. ; Bridgeman, J. S. ; Price, D. A. ; Sewell, A. K. ; Ueno, T. / Clonotypically similar hybrid αβ T cell receptors can exhibit markedly different surface expression, antigen specificity and cross-reactivity. In: Clinical and Experimental Immunology. 2015 ; Vol. 180, No. 3. pp. 560-570.
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