DEFECTIVE TCR EXPRESSION IN TRANSGENIC MICE CONSTRUCTED USING CDNA-BASED ALPHA-CHAIN AND BETA-CHAIN GENES UNDER THE CONTROL OF HETEROLOGOUSREGULATORY ELEMENTS

We describe the generation of ovalbumin (OVA)-specific, MHC class II-r estricted alpha beta T cell receptor (TCR) transgenic mice. Initial at tempts at generating these transgenic mice utilized heterologous regul atory elements to drive the expression of cDNA genes encoding the sepa rate alpha- and beta-chains of the TCR. Unexpectedly, T cells bearing the transgenic alpha beta TCR failed to emerge from the thymus in thes e mice, although the transgenes did modify endogenous TCR expression. However, subsequent modification of the approach which enabled express ion of the TCR beta-chain under the control of its natural regulatory elements generated mice whose peripheral T cells expressed the transge nic TCR and were capable of antigen-dependent proliferation. These res ults show that successful generation of MHC class II-restricted, OVA-s pecific alpha beta TCR transgenic mice was dependent upon combining cD NA- and genomic DNA-based constructs for expression of the respective alpha- and beta-chains of the TCR.