Recombination activating gene (RAG) 1 and RAG2 together catalyze V(D)J gene rearrangement in lymphocytes as the first step in the assembly and maturation of antigen receptors. RAG2 contains a plant homeodomain (PHD) near its C terminus (RAG2-PHD) that recognizes histone H3 methylated at lysine 4 (H3K4me) and influences V(D)J recombination. We report here crystal structures of RAG2-PHD alone and...

Studies of human NK cells and their role in tumor suppression have largely been restricted to in vitro experiments which lack the complexity of whole organisms, or mouse models which differ significantly from humans. In this study we showed that, in contrast to C57BL/6 Rag2(-/-)/gamma(c) (-/-) and NOD/Scid mice, newborn BALB/c Rag2(-/-)/gamma(c) (-/-) mice can support the development of human N...

scid disorder is major failure of the immune system, usually genetic. the aim of this study was on mutations detection of rag1, rag2, and il7rg genes in scid cases. mutation detection was performed by pcr sequencing. our results  indicated  that 13  mutations  were found  through  cases which  include 4 mutations in il7r gene (t661i, i138v, t56a, c57w), 7 mutations in rag1 (w896x, w204r, m324v,...

Epidermal hyperplasia is a protective response to restore disrupted skin barrier. Innate lymphoid cells (ILCs) have recently emerged as crucial resident immune for tissue homeostasis; however, how ILCs regulate the barrier after mechanical damage under physiological conditions remains unclear. In this study, we found that by mild tape stripping (T/S) induced epidermal with increased expression ...

The skin is enriched in immune cells, whose cell-cell communication with parenchymal cells support functions of the skin. Particularly, innate lymphoid (ILC) distribute to epithelium for immunosurveillance and bolster epithelial barrier. However, molecular mechanisms that ILC residency their functional interactions epithelia remain incompletely understood. Here, we performed single-cell RNA-seq...

During V(D)J recombination, recognition and cleavage of the recombination signal sequences (RSSs) requires the coordinated action of the recombination-activating genes 1 and 2 (RAG1/RAG2) recombinase complex. In this report, we use deletion mapping and site-directed mutagenesis to determine the minimal domains critical for interaction between RAG1 and RAG2. We define the active core of RAG2 req...

Loss of function mutations in the recombination activating genes RAG1 and RAG2 have been reported to cause a T-B-NK+ type of severe combined immunodeficiency. In addition identification of hypomorphic mutations in RAG1 and RAG2 has led to an expansion of the spectrum of disease to include Omenn syndrome, early onset autoimmunity, granuloma, chronic cytomegalovirus- or EBV-infection with expansi...

Although recent work has suggested that lymphopenia-induced homeostatic proliferation may improve T cell-mediated tumor rejection, there is little direct evidence isolating homeostatic proliferation as an experimental variable, and the mechanism by which improved antitumor immunity occurs via homeostatic proliferation is poorly understood. An adoptive transfer model was developed in which tumor...

RAG1 and RAG2 proteins catalyze site-specific DNA cleavage reactions in V(D)J recombination, a process that assembles antigen receptor genes from component gene segments during lymphocyte development. The first step towards the DNA cleavage reaction is the sequence-specific association of the RAG proteins with the conserved recombination signal sequence (RSS), which flanks each gene segment in ...