Hemizygous transgenic mice expressing only truncated class II A beta molecules lacking the 13 membrane distal residues were generated to address the role of class II cytoplasmic domains in physiological, non-transformed APC and in vivo immune responses. CD4+ T cell development and immune responses to conventional protein antigens, parasitic infections and skin grafts were indistinguishable between control and transgenic mice in vivo. However, in vitro, APC from transgenic mice poorly stimulate T cell hybridomas and wild-type in vivo-primed T cells. Class II-mediated induction of B7-1 expression and homotypic aggregation were not diminished in transgenic B cells, suggesting that both cAMP and tyrosine kinase signaling pathways remain intact despite truncation of the A beta cytoplasmic domain. The Jackson Laboratory 2024, used with permission.