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Publication : Transgenic mice with a diverse human T cell antigen receptor repertoire.

First Author  Li LP Year  2010
Journal  Nat Med Volume  16
Issue  9 Pages  1029-34
PubMed ID  20693993 Mgi Jnum  J:164445
Mgi Id  MGI:4833904 Doi  10.1038/nm.2197
Citation  Li LP, et al. (2010) Transgenic mice with a diverse human T cell antigen receptor repertoire. Nat Med 16(9):1029-34
abstractText  Because of tolerance mechanisms, it has been hard to identify the T cell receptors (TCRs) of high-avidity T cells against self (for example, tumor) antigens. TCRs that are specific for foreign human antigens from the nontolerant T cell repertoire can be identified in mice. Moreover, if mice are constructed to express the human TCR repertoire, they can be used to analyze the unskewed repertoire against human self antigens. Here we generated transgenic mice with the entire human TCRalphabeta gene loci (1.1 and 0.7 Mb), whose T cells express a diverse human TCR repertoire that compensates for mouse TCR deficiency. A human major histocompatibility class I transgene increases the generation of CD8+ T cells with human compared to mouse TCRs. Functional CD8+ T cells against several human tumor antigens were induced, and those against the Melan-A melanoma antigen used similar TCRs to those that have been detected in T cell clones from individuals with autoimmune vitiligo or melanoma. These mice will allow researchers to identify pathogenic and therapeutic human TCRs.
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