Major histocompatibility complex class I protein conformation altered by transmembrane potential changes.

The nature of charge distributions in membrane-bound macromolecular structures renders them susceptible to interaction with transmembrane potential fields. As a result, conformational changes in such species may be expected to occur when this potential is altered. We have detected reversible conformational change in the major histocompatibility complex (MHC) class I antigen in the plasma membrane of human JY cells, as monitored by flow-cytometric resonance energy-transfer, upon reduction of the transmembrane potential (depolarization). This change increased the intramolecular energy-transfer efficiency between fluorescent donor- and acceptor-labeled monoclonal antibodies directed, respectively, to epitopes on the light (beta 2-microglobulin) and the heavy chains of the MHC class I antigen. Repolarization of the depolarized samples restored the energy-transfer efficiency to the original values measured before depolarization. Depolarization caused similar relative changes in fluorescence resonance energy-transfer efficiency when Fab fragments were used for labeling MHC class I complex, suggesting that the observed phenomenon is not restricted to whole monoclonal antibodies.