title: Transgenic mice with a diverse human T cell antigen receptor repertoire.
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.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Liang-Ping
authors.initials: LP
authors.lastname: Li
authors.forename: J Christoph
authors.initials: JC
authors.lastname: Lampert
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Chen
authors.forename: Catarina
authors.initials: C
authors.lastname: Leitao
authors.forename: Jelena
authors.initials: J
authors.lastname: Popović
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Blankenstein
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005805:Genes, MHC Class I; D006801:Humans; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D050506:Mutant Chimeric Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic; D017384:Sequence Deletion; D014820:Vitiligo / Q000276:immunology
chemical_list: D001324:Autoantigens; D050506:Mutant Chimeric Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta