The function of HSP90 in MHC class II presentation (106.31)

Abstract

Abstract A role for heat shock proteins (HSP) in promoting antigen presentation via the MHC class I pathway is well established and appears to play a key role in host recognition of tumors and transformed cells. Studies suggest that some HSP may promote the presentation of cytoplasmic antigens via the class I pathway, as well as selecting cytoplasmic antigens for presentation in the context of MHC class II molecules. A role for intracellular HSP90 as well as HSC70 in regulating the presentation of a cytoplasmic autoantigen, glutamic acid decarboxylase (GAD) has been demonstrated in B lymphoblasts. Modulating intracellular expression of HSP90 alpha in human B lymphoblasts altered class II presentation of GAD epitopes. Yet, diminished cellular HSP90 alpha expression did not alter the steady state levels of GAD antigen, or disrupt the trafficking of this native antigen from the cytoplasm to membraneous intracellular organelles. This may suggest HSP90 acts after antigen processing to promote epitope transit into endosomal/lysosomal compartments. Prolonged knockdown of HSP90 alpha in B cells, lead to an increase in the expression of HSP90 beta subunit. Studies are currently underway to examine whether the activation state of B cells influences cytoplasmic antigen presentation as well as the role of HSP90 co-factors in regulating this pathway for class II presentation.