Disease relevance of LILRB2

• RESULTS: Recombinant LIR-2 (domains 1 and 2) was produced in E. coli and crystallized using streak seeding to optimize the crystal morphology [1].
• Interleukin-10 induces the upregulation of the inhibitory receptor ILT4 in monocytes from HIV positive individuals [2].

High impact information on LILRB2

• Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4 [3].
• We show here that CD8+CD28(-) alloantigen-specific T suppressor (TS) cells induce the up-regulation of ILT3 and ILT4 on monocytes and dendritic cells, rendering these antigen-presenting cells (APCs) tolerogenic [3].
• Immunoglobulin-like transcript 3 (ILT3) and ILT4 belong to a family of inhibitory receptors expressed by human monocytes and dendritic cells [3].
• On transfectants, HLA-G tetramers bound to inhibitory immunoglobulin-like transcript (ILT)2 and ILT4 receptors [4].
• Notably, LILRB1 cannot recognize the beta(2)m-free form of HLA-G or HLA-B27, but LILRB2 can recognize the beta(2)m-free form of HLA-B27 [5].

Biological context of LILRB2

• Analysis of mRNA from first trimester and term macrophages, as well as the monocyte cell line U937, resulted in amplicons of similar size to those expected for ILT2 and ILT4 [6].
• Human leukocyte Ig-like receptor B1 (LILRB1) and B2 (LILRB2) belong to "Group 1" receptors and recognize a broad range of major histocompatibility complex class I molecules (MHCIs) [7].
• Studies of human heart transplant recipients showed that rejection-free patients have circulating TS cells, which induce the up-regulation of ILT3 and ILT4 in donor APCs [3].
• Additionally, ILT4 transcription is tightly regulated by chromatin modifications accompanied by histone acetylation, which strictly controls expression within myeloid lineage cells [8].
• Reported is the identification of two single nucleotide polymorphisms within domain 1 (IgD1) of ILT4 at positions 113 and 144 [9].

Anatomical context of LILRB2

• Finally, we show that ILT2 and ILT4 effectively compete with CD8 for MHCI binding, raising the possibility that ILT2 modulates CD8+ T cell activation by blocking the CD8 binding as well as by recruiting inhibitory molecules through its immunoreceptor tyrosine-based inhibitory receptor motif [10].
• Sequence analysis of the amplicons revealed that the messages from decidual macrophages corresponded to ILT2 and ILT4 messages [6].
• The message amplified from the U937 cells using the ILT2 primers was also found to be identical to ILT2; however, sequence analysis revealed that the ILT4 message amplified from these cells is a truncated form of the message [6].
• HLA-G binds a limited repertoire of peptides and interacts with the inhibitory leukocyte Ig-like receptors LIR-1 and LIR-2 and possibly with certain natural killer cell receptors [11].
• LIR-2 is expressed by all monocytes and dendritic cells, whereas LIR-1 is additionally expressed by B cells and subsets of T and NK cells [12].

Physical interactions of LILRB2

• ILT2 generally bound with a 2- to 3-fold higher affinity than ILT4 to the same MHCI [10].
• Here, we report the 2.5-A resolution crystal structure of the LILRB2/HLA-G complex [5].

Regulatory relationships of LILRB2

• The synovium from patients with early RA showed extensive expression of the inhibitory LIR-2 and the activating LIR-7 on macrophages and neutrophils [13].

Other interactions of LILRB2

• We have used surface plasmon resonance to analyze the interaction of soluble forms of ILT4 and ILT2 with several MHCIs [10].
• Dual label flow cytometry confirmed the expression of ILT2 and ILT4 on CD14-positive first trimester decidual macrophages and U937 cells [6].
• These findings suggest that LIR-1 and LIR-2 function as unique MHC class I receptors involved in the inhibition or down-modulation of monocyte activation signals, particularly those mediated through the receptors for IgG, IgE and IgA [14].
• Tetrameric complexes of HLA-F also bound to ILT2 and ILT4 [15].
• In conclusion, the T cell costimulatory potential of human EC is markedly suppressed by IL-10 due to up-regulation of ILT3/ILT4, obviously not involving generation of Treg [16].

Analytical, diagnostic and therapeutic context of LILRB2

• Ligation of ILT4 receptor on DC from transgenic mice diminished peptide presentation by MHC class II molecules and significantly prolonged allograft survival [17].
• Addition of blocking antibodies against ILT3/ILT4 to EC/T cell cocultures resulted in nearly complete reestablishment of T cell proliferation [16].

References