Proteolytic cleavage of MHC class I by complement Cl-esterases - An overlooked mechanism?

The complement Cl-esterases have been shown to cleave the MHC class I molecules, which are important participants in the activation of T lymphocytes, between the alpha(2)- and the alpha(3)-domain of the heavy chain. The possible involvement of the Cl-esterases in the regulation of peripheral self-tolerance is discussed. It is hypothesized that the Cl-esterase-mediated cleavage of the MHC class I molecules either induces: a soluble fragment of the outer two domains of the MHC class I molecule, in association with beta(2)-microglobulin, to bind to the T cell receptors and prevent the cells from being activated, or produces a change in the exposure of the alpha(3)-domain that remain on the cell surface, acting as mediator of a 'veto signal' that prevents these cells from being activated.