In-Silico Approach to Study Affinities of NK Cell Inhibitory Receptor Interaction with Classical and Non -Classical MHC Ligands

Objective: Different classes of inhibitory receptors are present in each human NK cell. It has been seenthat NK inhibitory receptor and non-classical MHC interaction results into better inhibition of NK cell cytotoxicity than with classical MHC molecule, but the basis for this difference in inhibition potential of NK inhibitory receptors binding to classical and non-classical MHC proteins has remained unexplored. Since each NK cell expresses a multitude of receptors; it is difficult to study binding affinities and residues involved in receptor-ligands interaction through experimental studies.

Methods: The present work aims to investigate binding affinity of different inhibitory receptors with classical and non-classical MHC molecules and to explore important structural residues involved in the interactions through computational approach.

Results: Our results showed that there is high diversity of bonding in case of non-classical MHC binding to inhibitory receptors. Also, number of interface residues involved in interactions and presence of different chains were numerous in case of non-classical MHC molecules. A significantly higher number of H-bonds were observed in case of non-classical MHC interaction with inhibitory receptors.

Conclusion: Comparison between the affinities of inhibitory receptor with classical vs non-classical MHC molecules would give insights to correlate their influence on risk of cancer, therefore will help in devising promising NK- based immunotherapy.

Keywords: NK cell receptors, classical MHC, non-classical MHC, KIRs.