Leukocyte Function-Associated Antigen-1: Structure, Function and Application Prospects

Abstract

This review focuses on the structure, function and pathological role of leukocyte function-associated antigen-1 (LFA-1) which is a heterodimeric protein consisting of two subunits. LFA-1 plays a most important role in the immune system including adhesion, extravasation, migration, apoptosis, cytotoxicity, cytokine production, and proliferation of lymphocytes. Therefore, T-cell activation can be suppressed by blocking ICAM-1/LFA-1 interaction in autoimmune diseases and organ transplantation. Many different inhibitors (i.e. antibodies, peptides, small molecules) have been demonstrated to block ICAM-1/LFA-1 interaction, and some of them are promising for medical treatment or have reached clinical trials.

Cysteine protease cathepsin X modulates immune response via activation of β2 integrins

“…LFA-1 is expressed on all leucocytes and is involved in a broad range of immunological processes, such as leucocyte adhesion, extravasation, migration, antigen presentation, T-lymphocyte alloantigen-induced proliferation, 10 apoptosis, cytokine expression and cytotoxicity. 11 Mac-1 is expressed mainly on cells of myeloid lineage and plays an important role in phagocytosis, transendothelial migration of phagocytes, and the activation of neutrophils and monocytes. p150,95 is expressed by human monocytes, granulocytes, natural killer (NK) cells, and some lymphocytes, and can function as an adhesion molecule and interact with a counter-receptor on stimulated endothelium.…”

Helicobacter bilis Colonization Enhances Susceptibility to Typhlocolitis Following an Inflammatory Trigger

“…Examples of these upregulated genes included co-stimulatory molecules, such as Cd28, which promotes T cell activation/proliferation, and adaptor proteins such as Lcp2 (SLP-76) and Fyb, which interact with the Src family tyrosine kinase Fyn [27][28][29]. In addition, expression of the gene encoding integrin beta 2 chain (Itgb2/Cd18) was upregulated, which heterodimerizes with the integrin alpha L chain (encoded by ItgaL/ Cd11a) to form the co-stimulatory integrin lymphocyte function-associated antigen-1 (LFA-1) [30]. Interferonregulatory factor 4 (Irf4) was also found to be upregulated, a gene essential for the development of Th17 T cells [31].…”

LFA-1 on Leukemic Cells as a Target for Therapy or Drug Delivery

“…It also plays a key role in co-stimulation required for T cell activation. Accordingly, the functions of LFA-1 are relevant to most immunological diseases or symptoms such as inflammation, autoimmune diseases and graft rejection after organ transplantation (1, 10). The diseases are often typified by overexpression or deficiency of LFA-1.…”