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Transgenic mice with a diverse human T cell antigen receptor repertoire

Official URL:https://doi.org/10.1038/nm.2197
PubMed:View item in PubMed
Creators Name:Li, L.P. and Lampert, J.C. and Chen, X. and Leitao, C. and Popovic, J. and Mueller, W. and Blankenstein, T.
Journal Title:Nature Medicine
Journal Abbreviation:Nat Med
Volume:16
Number:9
Page Range:1029-1034
Date:September 2010
Keywords:Autoantigens, CD8-Positive T-Lymphocytes, MHC Class I Genes, Melanoma, Mutant Chimeric Proteins, Polymerase Chain Reaction, Antigen, T-Cell Receptors, Antigen, T-Cell, alpha-beta Receptors, Genetic Recombination, Sequence Deletion, Vitiligo, Animals, Mice
Abstract: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.
ISSN:1078-8956
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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