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). © 1996 Wiley‐Liss, Inc.