Adaptation of TCR expression vectors for the construction of mouse-human chimeric MBP-specific TCR transgenes.
T cell receptor (TCR) transgenic mice have been used extensively to study T cell development in vivo. Such studies have demonstrated high levels of expression of the TCR transgenes. Although a number of human T cell receptors appear to play a role in the development of autoimmune diseases, in vitro studies have proven inadequate for investigation of their putative pathogenicity. Several groups have reported the isolation of myelin basic protein (MBP)-reactive T cell clones from patients with multiple sclerosis and many of the T cell receptors from such clones have been well characterized. Since a number of inbred mouse strains have demonstrated susceptibility to a similar T cell-mediated inflammatory demyelinating disease known as EAE, a useful animal model is likely to be generated by expressing human MBP-specific TCR in susceptible mice. As a first step toward this goal we have cloned a number of TCR genes into an expression vector previously used for murine TCR genes. Here we report the development of a rapid cloning system for the generation of mouse-human chimeric TCR transgene constructs and the use of this system for the production of MBP-specific TCR transgenes. Human MBP-specific TCR transgenic mice will provide a unique system for the investigation of T cell-mediated demyelinating disease in the central nervous system (CNS).
Baker
A M
AM
Department of Neurology, Georgetown University Medical Center, Washington, DC 20007, USA.
Wang
Y
Y
Richert
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics* / Q000276:immunology*; D010957:Plasmids; D021382:Protein Sorting Signals / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D019076:Transgenes / Q000276:immunology
D004676:Myelin Basic Protein; D021382:Protein Sorting Signals; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins