BACKGROUND Lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18) is a cell adhesion molecule belonging to beta-2 integrin group with other two members Mac-1 (CD11b/CD18) and p150/CD18, which are herodimers with distinct alpha subunits of 150-180 kDa and same beta subunit of 95 kDa. It is expressed on T and B cells, granulocytes, and macrophages. LFA-1 adhesion is governed by its natural ligands including ICAM-1, 2, and 3, which are expressed on most leukocytes.1 It was also found that the IgSF member junctional adhesion molecule 1 (JAM-1) is also a LFA-1 ligand.2 LFA-1 participates in lymphocyte adhesion and activation, with prominent roles in the formation of the immunologic synapse and lymphocyte extravasation.3 Patients with leukocyte adhesion deficiency (LAD) disorder, a syndrome in which the LFA-1 integrin is mutated or missing, suffer severe recurrent bacterial infections and impaired overall immunity.
Stimulation of LFA-1 with antibodies or purified ICAMs induces augmentation of T-cell antigen receptor (TCR)-directed T-cell responsiveness. LFA-1 was shown to be linked to the tyrosine kinase signaling pathway that stimulates tyrosine phosphorylation and activation of phospholipase C-r1 (PLC-r1). Integrin beta-2 chain (CD18) crosslinking independently induced downstream mobilization of intracellular Ca2+ and potently costimulated TCR-induced Ca2+ flux with an increase in both amplitude and kinetics. Moreover, it was also demonstrated that LFA-1 induced the activation of src family kinases, Vav1 and p44/42 mitogen-activated protein kinase (MAPK), in human CD56+ NK cells. The LFA-1 signaling is directly linked to lymphocyte functional regulation.4 In addition, signaling through the LFA-1 integrin may affect c-Jun-driven transcription by regulating JAB1 nuclear localization. Disassociation of JAB-1 from LFA-1 is induced by phosphorylation at Ser745 on LFA-1 and mediates LFA-1-dependent c-Jun activation and subsequent AP-1 activity.5 After cell stimulation by phorbol ester or by CD3 ligation, the amino acids Thr758-Thr760 and Ser745 of LFA-1 become phosphorylated by PKC.
REFERENCES
1. Lub, M. et al: Immunol. Today 16:479-83, 1995
2. Ostermann, G. et al: Nature Immunol. 3:151-58, 2002
3. Kanner, S.B. et al: proc. Natl. Acad. Sci. USA 90:7099-7103, 1993
4. Perez, O.D. et al: Blood 104:1083-93, 2004
5. Bianchi, E. et al: Nature 404:617-21, 2000
Products are for research use only. They are not intended for human, animal, or diagnostic applications.
Cat.No.: | CG1286 |
Antigen: | Integrin beta-2 precursor recombinant protein epitope signature tag (PrEST). |
Isotype: | Rabbit IgG |
Species & predicted species cross- reactivity ( ): | Human |
Applications & Suggested starting dilutions:* | WB 1:100-1:250 IP n/d IHC 1:200-1:500 ICC n/d FACS n/d |
Predicted Molecular Weight of protein: | 29 kDa |
Specificity/Sensitivity: | Detects endogenous Integrin-β2/LFA-1β proteins without cross-reactivity with other family members. |
Storage: | Store at -20°C, 4°C for frequent use. Avoid repeated freeze-thaw cycles. |
*Optimal working dilutions must be determined by end user.