Journal article
Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptors
Communications Biology, Vol.5(1), Art. 133
2022
Abstract
Pre-existing pathogen-specific memory T cell responses can contribute to multiple adverse outcomes including autoimmunity and drug hypersensitivity. How the specificity of the T cell receptor (TCR) is subverted or seconded in many of these diseases remains unclear. Here, we apply abacavir hypersensitivity (AHS) as a model to address this question because the disease is linked to memory T cell responses and the HLA risk allele, HLA-B*57:01, and the initiating insult, abacavir, are known. To investigate the role of pathogen-specific TCR specificity in mediating AHS we performed a genome-wide screen for HLA-B*57:01 restricted T cell responses to Epstein-Barr virus (EBV), one of the most prevalent human pathogens. T cell epitope mapping revealed HLA-B*57:01 restricted responses to 17 EBV open reading frames and identified an epitope encoded by EBNA3C. Using these data, we cloned the dominant TCR for EBNA3C and a previously defined epitope within EBNA3B. TCR specificity to each epitope was confirmed, however, cloned TCRs did not cross-react with abacavir plus self-peptide. Nevertheless, abacavir inhibited TCR interactions with their cognate ligands, demonstrating that TCR specificity may be subverted by a drug molecule. These results provide an experimental road map for future studies addressing the heterologous immune responses of TCRs including T cell mediated adverse drug reactions.
Details
- Title
- Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptors
- Authors/Creators
- A. Sooda (Author/Creator)F. Rwandamuriye (Author/Creator)C.N. Wanjalla (Author/Creator)L. Jing (Author/Creator)D.M. Koelle (Author/Creator)B. Peters (Author/Creator)S. Leary (Author/Creator)A. Chopra (Author/Creator)M.A. Calderwood (Author/Creator)S.A. Mallal (Author/Creator)R. Pavlos (Author/Creator)M. Watson (Author/Creator)E.J. Phillips (Author/Creator)A.J. Redwood (Author/Creator)
- Publication Details
- Communications Biology, Vol.5(1), Art. 133
- Publisher
- Nature Research
- Identifiers
- 991005540568007891
- Copyright
- © 2022 The Authors.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.265 Dermatology - Skin Allergies
- 1.265.1140 Drug Hypersensitivity
- Web Of Science research areas
- Biology
- ESI research areas
- Biology & Biochemistry