Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals.
Authors: Moir S, Ho J, Malaspina A, Wang W, DiPoto AC, OShea MA, Roby G, Kottilil S, Arthos J, Proschan MA, Chun TW, Fauci AS
J. Exp. Med., 2008;205(8):1797-805.
Species: Human
Sample Type: Whole Cells
Application: Flow

The immunoglobulin-like transcript (ILT) family of activating and inhibitory type immunoreceptors are expressed on many leukocyte subsets and function in the regulation of immune responses (1‑3). This family was also named leukocyte Ig-like receptors (LIR) and monocyte/macrophage Ig-like receptors (MIR). ILTs share significant homology with killer cell Ig-like receptors (KIR). The ILT genes are located on human chromosome 19q13.4 in the leukocyte receptor complex, which also include the genes encoding KIRs (4). With the exception of ILT-6, which is a soluble molecule, all ILT family members are type I transmembrane proteins having two or four extracellular Ig-like domains (2, 3). One subset of the ILT receptors (referred to as subfamily B of the LIRs) has long cytoplasmic tails containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that inhibit signaling events by recruiting SH2-containing protein tyrosine phosphatase-1. Another subset of the ILT receptors (referred to as subfamily A of the LIRs) contains activating receptors with short cytoplasmic regions that lack signal transduction motifs. These receptors contain a basic arginine residue within their transmembrane domains, which allows association with Fc R gamma, an immunoreceptor tyrosine-based activation motif (ITAM)-bearing signal adapter protein (1‑3). ILT2, also known as LIR1, MIR7, and CD85j, is expressed on most monocytes, dendritic cells, and mature B cells (1‑3). It is also expressed on small percentages of T cells and NK cells. ILT2 has four extracellular Ig-like domains and three cytoplasmic ITIMs. It functions as an inhibitory receptor that prevents cellular activation. ILT2 has been shown to bind classical (HLA-A and -B) and nonclassical (HLA-G1, -E and -F) MHC class I molecules (MHCI) (1‑3). ILT2 also binds with high affinity to an MHC class I homologue from human cytomegalovirus (3). Ligation of ILT2 by MHC class I may function to poise cellular activation thresholds and inhibit various leukocyte effector mechanisms that are regulated by MHC class I molecules on target cells.

1. Allen, D. et al. (2000) Immunobiol. 202:34.
2. Colonna, M. et al. (1999) J. Leukocyte Biol. 66:375.
3. Borges, L. and D. Cosman (2000) Cytokine Growth Factor Rev. 11:209.
4. Young, N. et al. (2001) Immunogenetics 53:270.