Molecular flexibility can influence the stimulatory ability of receptor-ligand interactions at cell-cell junctions

Proceedings of the National Academy of Sciences of the United States of America
Shuyan QiArup K Chakraborty

Abstract

Direct cell-cell communication is crucial for many processes in biology, particularly embryogenesis, interactions between hematopoetic cells, and in the nervous system. This communication is often mediated by the binding of receptors to cognate ligands at a cell-cell junction. One such interaction that is very important for the development of many immune responses is the binding of the alphabeta T cell receptor for antigen (TCR) on T lymphocytes with peptide-MHC complexes on other cells. In general, the stability (e.g., half-life) of TCR-peptide-MHC binding measured in solution correlates with functional responses. Several anomalies have been reported, however. For example, for some anomalous ligands, large changes in heat capacity can apparently substitute for a lack of stability in TCR-ligand interactions. Here, we show that, when there are significant conformational changes during receptor-ligand binding and the receptor/ligand have relatively rigid molecular subdomains, the difference between the half-life of this receptor-ligand complex at a cell-cell junction and that measured using soluble molecules is large. Thus, receptors/ligands with these specific molecular features do not follow correlations between stimulatory pot...Continue Reading

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