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).