Disease relevance of KLRG1

• Over 92% of CD8(+) cells specific for CMV or EBV expressed KLRG1 during the latent stage of these chronic infections [1].
• Using multiparameter flow cytometry, we studied KLRG1 expression on CD8(+) T cells specific for epitopes of CMV, EBV, influenza, and HIV [1].
• We found that repetitive and persistent antigen stimulation leads to an increase in KLRG1 expression of virus-specific CD8+ T cells in mice and that virus-specific CD8+ T cells are mostly KLRG1+ in chronic human viral infections (human immunodeficiency virus, cytomegalovirus, and Epstein-Barr virus) but not in resolved infection (influenza virus) [2].
• Analysis of CD127 and KLRG1 Expression on Hepatitis C Virus-Specific CD8+ T Cells Reveals the Existence of Different Memory T-Cell Subsets in the Peripheral Blood and Liver [3].
• AIMS/HYPOTHESIS: Effects of the transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA) on the regulation of beta cell gene expression and function were investigated [4].

High impact information on KLRG1

• By using a newly generated monoclonal antibody specific for human KLRG1, we now demonstrate that expression of KLRG1 also identifies T cells in humans that are capable of secreting cytokines but that fail to proliferate after stimulation [5].
• Besides T cells, a significant portion (approximately 50%) of human natural killer (NK) cells expressed KLRG1 [5].
• Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1) [5].
• We further observed that CD8(+) cells expressing CD57, a marker of replicative senescence, also expressed KLRG1; however, a population of CD57(-)KLRG1(+) cells was also identified [1].
• Glucose influenced DNA-binding activity of MAFA in rat islets in a bell-shaped manner [4].

Biological context of KLRG1

• In contrast to T cells in adult, KLRG1(+) T cells in cord blood exhibited predominantly a naive CCR7(+)CD45RA(+) and CD11a(low) phenotype [6].
• Here we report the complete nucleotide sequence, alternatively spliced variants, and the physical mapping of the KLRG1 gene in the mouse [7].
• Genomic structure, alternative splicing, and physical mapping of the killer cell lectin-like receptor G1 gene (KLRG1), the mouse homologue of MAFA [7].
• In contrast to human KLRG1 and to the murine KLR family members, mouse KLRG1 locates outside the NK complex on Chromosome 6 between the genes encoding CD9 and CD4 [7].
• However, in contrast to rat MAFA, the amino acid sequence suggests the presence of two additional extracellular N-linked glycosylation sites [8].

Anatomical context of KLRG1

• CD8(+) T cell cells specific for HIV epitopes were mostly (72-89%) KLRG1(+), even though not quite at the level of predominance noted with CMV or EBV [1].
• Killer cell lectin-like receptor G1 (KLRG1) is one of several inhibitory killer cell lectin-like receptors expressed by NK cells and T lymphocytes, mainly CD8(+) effector/memory cells that can secrete cytokines but have poor proliferative capacity [1].
• Thus, analysis of KLRG1 expression in cord blood revealed an unexpected heterogeneity of human T cells in newborns [6].
• Similar to other inhibitory NK cell receptors, KLRG1 expression in adult peripheral blood lymphocytes is restricted to NK cells and to antigen-experienced T cells [6].
• In vivo, pathogenic immune system activation induces dramatic changes in the expression patterns of KLRG1 among the different cell subsets [9].

Associations of KLRG1 with chemical compounds

• The human MAFA-like receptor (MAFA-L) and the rat MAFA protein are expressed by basophils and both have an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic tail, consistent with an inhibitory role in basophil activation [10].

Regulatory relationships of KLRG1

• Surprisingly, we identified substantial subsets of CD4 ( approximately 30%) and CD8 ( approximately 20%) alphabeta T cells in cord blood that expressed KLRG1 [6].

Other interactions of KLRG1

• However, the recent identification of non-MHC class I ligands for inhibitory immune receptors, such as KLRG1, KLRB1 and LAIR-1, indicates that also MHC class I-independent inhibitory immune receptors play crucial roles in inducing peripheral tolerance [11].
• Importantly, the expression profiles of the interleukin-7 receptor alpha chain (CD127) and the killer cell lectin-like receptor G1 (KLRG1) have been shown to be differentially influenced by repetitive T-cell receptor interactions [3].

Analytical, diagnostic and therapeutic context of KLRG1

• Epitope mapping localized the 2F1 epitope to three noncontiguous regions of the IpaB protein within the alpha-helical domain that contains homology with myosin [12].

References