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Naisbitt, D.J., Britschgi, M., Wong, G., Farrell, J., Depta, J.P., et al. (2003) Hypersensitivity reactions to carbamazepine: Characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones. Molecular Pharmacology, 63, 732-741.

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• TITLE: T cell receptor variable β20-1 harbors a nucleotide binding pocket in the CDR2β loop

  AUTHORS: Stephan Watkins, Werner J. Pichler

  KEYWORDS: T Cell Receptor; T Cell Receptor Variable Domain; Adverse Drug Reactions; Autoimmune Diseases

  JOURNAL NAME: Open Journal of Immunology, Vol.3 No.3, September 20, 2013

  ABSTRACT: Novel aspects of T cells containing TCRVβ20-1 are numerous, ranging from pathogen specific reactivity to specific tissue homing, or possible T cell subsets. Recently, it was demonstrated that TCR itself could become reactive by binding to small molecules free of the pHLA interface. Our work here was to identify a natural ligand binding to an identified pocket on the CDR2β loop of these TCR. Using docking of suspected ligands, we were able to show Guanine and Adenine diand tri-nucleotides readily bind to the identified site. Comparing these with small molecule sites found on other TCR types, we show this interaction is novel. With further molecular dynamic simulations, these sites are shown to be plausible by conducting simple computational based solubility tests as cross validation. Combined with simple proliferative responses, the identified nucleotides are also shown to have functional consequences by inducing T cell proliferation for CD4/Vβ20-1 + T cells, while failing to induce proliferation in other T cell isolates. Merging computational and simple cell assays, this work establishes a role of nucleotides in T cells found to contain this TCR subtype.