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 st udy T cell development in vivo, Such studies have demonstrated high le vels 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 o f their putative pathogenicity, Several groups have reported the isola tion of myelin basic protein (MBP)-reactive T cell clones from patient s with multiple sclerosis and many of the T cell receptors from such c lones have been well characterized, Since a number of inbred mouse str ains have demonstrated susceptibility to a similar T cell-mediated inf lammatory demyelinating disease known as EAE, a useful animal model is likely to be generated by expressing human MBP-specific TCR in suscep tible mice, As a first step toward this goal we have cloned a number o f TCR genes into an expression vector previously used for murine TCR g enes, Here we report the development of a rapid cloning system for the generation of mouse-human chimeric TCR transgene constructs and the u se of this system for the production of MBP-specific TCR transgenes. H uman MBP-specific TCR transgenic mice will provide a unique system for the investigation of T cell-mediated demyelinating disease in the cen tral nervous system (CNS). (C) 1996 Wiley-Liss, Inc.