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Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR α-chains present among genetically unrelated patients with tuberculosis. The(More)
Active-site directed probes are powerful in studies of enzymatic function. We report an active-site directed probe based on a warhead so far considered unreactive. By replacing the C-terminal carboxylate of ubiquitin (Ub) with an alkyne functionality, a selective reaction with the active-site cysteine residue of de-ubiquitinating enzymes was observed. The(More)
CD1 activates T cells, but the function and size of the possible human T cell repertoires that recognize each of the CD1 antigen-presenting molecules remain unknown. Using an experimental system that bypasses major histocompatibility complex (MHC) restriction and the requirement for defined antigens, we show that polyclonal T cells responded at higher rates(More)
Post-translational modification of proteins with ubiquitin (Ub) and Ub chains controls protein breakdown by the proteasome, cellular localization of proteins, transcriptional activity, and DNA repair. [1] Ubiquitin is a highly conserved 76 amino acid protein that can be linked to target proteins through an isopeptide bond between the C-terminal carbox-ylate(More)
T cells autoreactive to the antigen-presenting molecule CD1a are common in human blood and skin, but the search for natural autoantigens has been confounded by background T cell responses to CD1 proteins and self lipids. After capturing CD1a-lipid complexes, we gently eluted ligands while preserving non-ligand-bound CD1a for testing lipids from tissues.(More)
Microbial lipids activate T cells by binding directly to CD1 and T cell receptors (TCRs) or by indirect effects on antigen-presenting cells involving induction of lipid autoantigens, CD1 transcription, or cytokine release. To distinguish among direct and indirect mechanisms, we developed fluorescent human CD1b tetramers and measured T cell staining. CD1b(More)
In the context of large and ever growing archives, generating annotation suggestions automatically from textual resources related to the documents to be archived is an interesting option in theory. It could save a lot of work in the time-consuming and expensive task of manual annotation and it could help cataloguers attain a higher inter annotator(More)
CD1c is expressed with high density on human dendritic cells (DCs) and B cells, yet its antigen presentation functions are the least well understood among CD1 family members. Using a CD1c-reactive T cell line (DN6) to complete an organism-wide survey of M. tuberculosis lipids, we identified C32 phosphomycoketide (PM) as a previously unknown molecule and a(More)
Audiovisual material is a vital component of the world's heritage but it remains diffi cult to access. With the Netherlands Institute for Sound and Vision as one of its partners, the MuNCH project aims to investigate new methods for improving access to a wide range of audiovisual documents. MuNCH brings together three research fi elds: multimedia analysis,(More)
Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present(More)