TY - JOUR
T1 - Understanding TR binding to pMHC complexes
T2 - how does a TR scan many pMHC complexes yet preferentially bind to one
AU - Khan, Javed Mohammed
AU - Ranganathan, Shoba
N1 - Copyright the Author(s) 2011. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2011
Y1 - 2011
N2 - Understanding the basis of the binding of a T cell receptor (TR) to the peptide-MHC (pMHC) complex is essential due to the vital role it plays in adaptive immune response. We describe the use of computed binding (free) energy (BE), TR paratope, pMHC epitope, molecular surface electrostatic potential (MSEP) and calculated TR docking angle (θ) to analyse 61 TR/pMHC crystallographic structures to comprehend TR/pMHC interaction. In doing so, we have successfully demonstrated a novel/rational approach for θ calculation, obtained a linear correlation between BE and θ without any "codon" or amino acid preference, provided an explanation for TR ability to scan many pMHC ligands yet specifically bind one, proposed a mechanism for pMHC recognition by TR leading to T cell activation and illustrated the importance of the peptide in determining TR specificity, challenging the "germline bias" theory.
AB - Understanding the basis of the binding of a T cell receptor (TR) to the peptide-MHC (pMHC) complex is essential due to the vital role it plays in adaptive immune response. We describe the use of computed binding (free) energy (BE), TR paratope, pMHC epitope, molecular surface electrostatic potential (MSEP) and calculated TR docking angle (θ) to analyse 61 TR/pMHC crystallographic structures to comprehend TR/pMHC interaction. In doing so, we have successfully demonstrated a novel/rational approach for θ calculation, obtained a linear correlation between BE and θ without any "codon" or amino acid preference, provided an explanation for TR ability to scan many pMHC ligands yet specifically bind one, proposed a mechanism for pMHC recognition by TR leading to T cell activation and illustrated the importance of the peptide in determining TR specificity, challenging the "germline bias" theory.
UR - http://www.scopus.com/inward/record.url?scp=79952045349&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0017194
DO - 10.1371/journal.pone.0017194
M3 - Article
C2 - 21364947
AN - SCOPUS:79952045349
SN - 1932-6203
VL - 6
SP - 1
EP - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e17194
ER -