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The RAG1 endonuclease, together with its cofactor RAG2, is essential for V(D)J recombination but is a potent threat to genome stability. The sources of RAG1 mis-targeting and the mechanisms that have evolved to suppress it are poorly understood. Here, we report that RAG1 associates with chromatin at thousands of active promoters and enhancers in the genome(More)
The main adaptive immune response to bacteria is mediated by B cells and CD4+ T-cells. However, some bacterial proteins reach the cytosol of host cells and are exposed to the host CD8+ T-cells response. Both gram-negative and gram-positive bacteria can translocate proteins to the cytosol through type III and IV secretion and ESX-1 systems, respectively. The(More)
Viruses employ various means to evade immune detection. Reduction of CD8(+) T cell epitopes is one of the common strategies used for this purpose. Hepatitis B virus (HBV), a member of the Hepadnaviridae family, has four open reading frames, with about 50% overlap between the genes they encode. We computed the CD8(+) T cell epitope density within HBV(More)
Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes. We performed exome and whole-genome DNA sequencing and RNA sequencing on purified CTCL and matched normal cells. The results implicate mutations in 17 genes in CTCL pathogenesis, including genes involved in T cell activation and apoptosis, NF-κB signaling, chromatin(More)
Rapidly mutating viruses such as the hepatitis C virus (HCV), the human immunodeficiency virus (HIV), or influenza viruses (Flu) call for highly effective universal peptide vaccines, i.e. vaccines that do not only yield broad population coverage but also broad coverage of various viral strains. The efficacy of such vaccines is determined by multiple(More)
Predictive tools for all levels of CD8+ T cell epitopes processing have reached a maturation level. Good prediction algorithms have been developed for proteasomal cleavage, TAP and MHC class I peptide binding. The same cannot be said of CD4+ T cell epitopes. While multiple algorithms of varying accuracy have been proposed for MHC class II peptide binding,(More)
The RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also binds to thousands of places outside of these loci. RAG2 localizes directly to lysine 4 trimethylated histone 3 (H3K4me3) through a plant homeodomain (PHD) finger. The relative contribution of RAG2-dependent and RAG1-intrinsic mechanisms in determining RAG1 binding(More)
Incremental selection within a population, defined as limited fitness changes following mutation, is an important aspect of many evolutionary processes. Strongly advantageous or deleterious mutations are detected using the synonymous to non-synonymous mutations ratio. However, there are currently no precise methods to estimate incremental selection. We here(More)
The relation between the complexity of organisms and proteins and their evolution rates has been discussed in the context of multiple generic models. The main robust claim from most such models is the negative relation between complexity and the accumulation rate of mutations. Viruses accumulate escape mutations in their epitopes to avoid detection and(More)
Viral epitopes have a distinct codon usage that reflects their dual role in infection and immunity. On the one hand, epitopes are part of proteins important to viral function; on the other hand, they are targets of the immune response. Studies of selection are most commonly based on changes of amino acid and seen through the accumulation of non-synonymous(More)