Abstract
The thymic development and peripheral activation of CD4+ T cells are critically dependent upon interactions with MHC class II molecules on the surface of antigen presenting cells (APC). In vitro studies involving transfection of cell lines with mutant MHC molecules have demonstrated that the cytoplasmic domains of class II molecules can be required for efficient antigen presentation. To address the role of class II cytoplasmic domains in physiological, non-transformed APC and in vivo immune responses, we have generated transgenic mice which express only truncated class II A beta molecules lacking the 13 membrane distal residues. In vivo, CD4+ T cell development and immune responses to conventional protein antigens, parasitic infections and skin grafts were indistinguishable between control and transgenic mice. Nevertheless, in vitro, APC from transgenic mice poorly stimulate T cell hybridomas and wild-type in vivo-primed T cells. Neither class II-mediated induction of B7-1 expression nor homotypic aggregation were diminished in transgenic B cells, suggesting that both cAMP and tyrosine kinase signaling pathways remain intact despite truncation of the A beta cytoplasmic domain. Furthermore, chemically-fixed cells from transgenic...Continue Reading
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