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.