LILRB1

Protein LILRB1 PDB 1g0x

LILRB1 (Leukocyte Immunoglobulin-Like Receptor B1), also known as ILT2 (Immunoglobulin-Like Transcript 2), is a protein that in humans is encoded by the LILRB1 gene. This receptor belongs to a family of receptors known as the Leukocyte Immunoglobulin-Like Receptors (LILRs), which are present on the surfaces of immune cells such as monocytes, dendritic cells, B cells, and subsets of T cells and natural killer (NK) cells. LILRB1 plays a critical role in the regulation of immune responses, particularly in the inhibition of immune cell activation.

Function

LILRB1 is an inhibitory receptor that recognizes class I Major Histocompatibility Complex (MHC) molecules. Upon binding to MHC class I molecules on target cells, LILRB1 transmits inhibitory signals into the immune cell, leading to the downregulation of immune responses. This interaction is crucial for maintaining tolerance to self-antigens and preventing autoimmune diseases. Additionally, LILRB1 is involved in the modulation of other immune processes, including the regulation of antibody production by B cells and the suppression of cytotoxic functions of NK cells and T cells.

Structure

The LILRB1 protein is composed of several immunoglobulin-like domains in its extracellular region, a transmembrane domain, and a cytoplasmic tail that contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The ITIMs are essential for the receptor's inhibitory function, as they recruit phosphatases upon phosphorylation, which then dephosphorylate key signaling molecules, leading to the inhibition of cell activation.

Clinical Significance

The expression and function of LILRB1 have been implicated in various clinical conditions, including autoimmune diseases, infectious diseases, and cancer. In autoimmune diseases, the dysregulation of LILRB1 expression or function can contribute to the loss of tolerance to self-antigens and the development of autoimmunity. In the context of infectious diseases, some pathogens have evolved mechanisms to exploit LILRB1 to evade immune detection and destruction. For example, certain viruses express proteins that mimic MHC class I molecules, binding to LILRB1 and inhibiting immune responses against the virus. In cancer, tumor cells can upregulate MHC class I expression to engage LILRB1 on immune cells, thereby inhibiting anti-tumor immunity and facilitating tumor escape from immune surveillance.

Research Directions

Research on LILRB1 is focused on understanding its role in the immune system and its implications in diseases. This includes studying the receptor's signaling pathways, identifying its ligands, and exploring its interactions with other immune receptors. Additionally, there is interest in targeting LILRB1 for therapeutic purposes, such as developing inhibitors to block its interaction with MHC class I molecules in cancer therapy or designing agonists to enhance its inhibitory function in autoimmune diseases.