By Ian Kimber, Marc Pallardy (auth.), Stefan F. Martin (eds.)
This publication summarizes the state-of-the artwork within the improvement of T cell-based in vitro assays, which supply beneficial instruments for danger id, hazard evaluate and development of diagnostics. it is going to be of curiosity to scientists, the chemical and pharmaceutical undefined, and regulators taken with the substitute of animal trying out methods.
The id of detrimental chemical compounds and medication is vital to making sure human wellbeing and fitness. The ban on animal trying out for the cosmetics seeing that 2009 and foreign efforts to lessen and exchange animal checking out in study and immunotoxicology demand replacement in vitro tools. the main particular immune reaction to chemical substances and medicine that reason allergic touch dermatitis, respiration disorder and hostile drug reactions is the hugely antigen-specific T lymphocyte reaction. hence using T cells as instruments for deciding upon touch allergens and medication which could reason illnesses is of significant curiosity.
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Additional resources for T Lymphocytes as Tools in Diagnostics and Immunotoxicology
It is conceivable that most of the T cells involved in chemical-induced allergies recognize the chemical. However, it is possible that T cells primed by haptenated peptides may also react to the unmodified self-peptide. Such reactivities may underlie the vitiligo associated with melanoma therapy using the topical application of the contact sensitizers DNCB or DPCP. In that case the reactivity of cytotoxic T cells to unmodified self-peptides resulted in the killing of healthy melanoma cells resulting in depigmentations as a side effect observed in this therapy (Henderson and Ilchyshyn 1995).
It was shown that the TCR Vβ CDR3 region interacted especially with a conserved lysine residue present in position 7 of the DR52c-binding nonameric peptides, and it was suggested that this lysine mimics Ni in the natural TCR ligand. The CDR3 loop extends into the region of the DR52c to interact with conserved residues in a panel of mimotope peptides and residues of the DR52c α1 and β1 helices. Interestingly, an aspartic acid residue was crucial for the peptide recognition and could not be replaced by a glutamic acid residue.
Besides resulting in long-lived, easy to culture cell lines, this system allowed the systematic mutation of the antigen-binding CDR3 regions in TCR α- and β-chains and, hence, the localization of contact sites for nickel in TCR and HLA protein. These studies revealed two principally different ways of TCR interactions with Ni plus HLA: for one TCR, Lu et al, indeed, showed the combination of defined peptide and HLA haplotype to be essential for Ni recognition (Lu et al. 2003). However, a different TCR recognized nickel HLA haplotype specific but apparently independent of the nature of associated peptides (Gamerdinger et al.
T Lymphocytes as Tools in Diagnostics and Immunotoxicology by Ian Kimber, Marc Pallardy (auth.), Stefan F. Martin (eds.)