LFA-1 fine-tuning by cathepsin X

• Published in: IUBMB life Vol. 63; no. 9; p. 686
• Main Authors: Jevnikar, Zala, Obermajer, Nataša, Kos, Janko
• Format: Journal Article
• Language: English
• Published: England 01.09.2011
• Subjects: Actinin - metabolism; Cathepsins - metabolism; Cell Adhesion; Cell Movement - immunology; Immunologic Surveillance - immunology; Lymphocyte Function-Associated Antigen-1 - immunology; Lymphocyte Function-Associated Antigen-1 - metabolism; Protein Binding; Protein Conformation; T-Lymphocytes - immunology; Talin - metabolism
• ISSN: 1521-6551
• DOI: 10.1002/iub.505

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 β (2) subunit. Cathepsin X, a cysteine carboxypeptidase, promotes T-cell migration and morphological changes by cleaving the β (2) cytoplasmic tail of LFA-1. In this way, it modulates the affinity of LFA-1 for structural adaptors talin-1 and α-actinin-1 and enables the stepwise transition between intermediate and high-affinity conformations of LFA-1, 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-LFA-1 therapy.