LFA‐1 fine‐tuning by cathepsin X

• Published in: IUBMB life 2011-09, Vol.63 (9), p.686-693
• Main Authors: Jevnikar, Zala, Obermajer, Nataša, Kos, Janko
• Format: Article
• Language: English
• Subjects: Actinin - metabolism; carboxypeptidase; Cathepsins - metabolism; Cell Adhesion; Cell Movement - immunology; Immunologic Surveillance - immunology; LFA‐1 affinity; Lymphocyte Function-Associated Antigen-1 - immunology; Lymphocyte Function-Associated Antigen-1 - metabolism; Protein Binding; Protein Conformation; T-Lymphocytes - immunology; talin; Talin - metabolism; T‐cell; α‐actinin; β2 cytoplasmic tail
• ISSN: 1521-6543; 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. © 2011 IUBMB IUBMB Life, 63(9): 686–693, 2011