What is another function of LFA-1 on naive T cells?
LFA-1 and T Cell Memory Development As described above, LFA-1 plays a critical role in facilitating naïve T cell activation and differentiation through T cell-APC contacts. Indeed, defects in LFA-1/ICAM-1 interactions have been shown to lead to impairment of memory formation (122, 123).
What is the normal function of the integrin LFA-1?
LFA-1 is an integrin, which means it functions primarily as an adhesion molecule promoting contact either between two cells or between a cell and the extracellular matrix.
Is LFA-1 a receptor?
Consequently, the LFA-1 receptor is activated and binds to its ligand, ICAM-1, on the endothelium. Thus, the Rap1–RIAM–Talin inside-out signaling axis plays an essential role in the regulation of LFA-1 activation and adhesion strength between T cell and endothelium and subsequent migration of the T lymphocyte.
Is LFA-1 on T cells?
LFA-1 is a key T cell integrin that plays a critical role in the regulation of these functions. With this highly diverse set of roles, it is unsurprising that LFA-1 has been implicated in numerous autoimmune and inflammatory conditions including inflammatory bowel disease, psoriasis, diabetes, and arthritis (1, 2).
What is ICAM in immunology?
The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells.
What is the ligand for the integrin LFA-1?
Inflammatory recruitment of leukocytes is governed by dynamic interactions between integrins and endothelial immunoglobulin superfamily (IgSF) proteins. We have identified the IgSF member junctional adhesion molecule 1 (JAM-1) as a ligand of the beta(2) integrin lymphocyte function-associated antigen 1 (LFA-1).
What are the lymphocytes function?
Lymphocytes are white blood cells uniform in appearance but varied in function and include T, B, and natural killer cells. These cells are responsible for antibody production, direct cell-mediated killing of virus-infected and tumor cells, and regulation of the immune response.
What does LFA-1 stand for?
Lymphocyte function-associated antigen 1 (LFA-1) is an integrin found on lymphocytes and other leukocytes. LFA-1 plays a key role in emigration, which is the process by which leukocytes leave the bloodstream to enter the tissues. LFA-1 also mediates firm arrest of leukocytes.
What produces ctla4?
CTLA-4 is also found in regulatory T cells (Tregs) and contributes to their inhibitory function. T cell activation through the T cell receptor and CD28 leads to increased expression of CTLA-4.
Is ICAM-1 an integrin?
ICAM-1 is a ligand for LFA-1 (integrin), a receptor found on leukocytes. When activated, leukocytes bind to endothelial cells via ICAM-1/LFA-1 and then transmigrate into tissues.
How does LFA-1 activate inside out signaling?
The process of activating LFA-1 is known as inside out signaling, which causes LFA-1 to shift from low affinity to high affinity by opening the ligand-binding site. Early discovery of cellular adhesion molecules involved the use of monoclonal antibodies to inhibit cellular adhesion processes.
What are the ligands of LFA-1?
As of 2007, LFA-1 has 6 known ligands: ICAM-1, ICAM-2, ICAM-3, ICAM-4, ICAM-5, and JAM-A. LFA-1/ICAM-1 interactions have recently been shown to stimulate signaling pathways that influence T cell differentiation. LFA-1 belongs to the integrin superfamily of adhesion molecules.
What is LFA1 engagement in T cells?
During T cell migration, LFA-1 engagement is primarily utilized in two-dimensional spaces. One study found that neither LFA-1 nor α 4 integrins support stable adhesions of naive T cells to neighboring T cells, DCs or stroma in the lymph node T cell zones (64).
What is the role of LFA-1 in memory generation and differentiation?
This study further demonstrated that the unequal inheritance of LFA-1 plays an important role in memory generation and differentiation of T cells into both effector and memory subsets. Recent evidence suggests a role for LFA-1 as a mechanosensor affecting cell signaling and integrin activation through the force generated by ligand binding.