LFA-1 Fine-tuning by Cathepsin X

The adhesion molecule lymphocyte function-associated antigen (LFA)-1 plays a key role in immune surveillance and response. Its conformation is spatially and temporally regulated, enabling adhesion and deadhesion during T-cell migration. LFA-1 adhesion to its major ligand intercellular adhesion molecule 1 is controlled by adaptor proteins which bind the cytoplasmic tail of the beta(2) subunit. Cathepsin X, a cysteine carboxypeptidase, promotes T-cell migration and morphological changes by cleaving the beta(2) cytoplasmic tail of LFA-1. In this way, it modulates the affinity of LFA-1 for structural adaptors talin-1 and alpha-actinin-1 and enables the stepwise transition between intermediate and high-affinity conformations of LEA-I, an event that is necessary for effective T-cell function. Cathepsin X regulation that would allow precise modulation of LFA-1 affinity has a great potential for anti-LEA-1 therapy. (C) 2011 IUBMB Life, 63(9): 686-693,2011