INHIBITION OF THE MHC CLASS II ANTIGEN PRESENTATION PATHWAY AND PRESENTATION TO CD4+ CELLS

摘要

The human cytomegalovirus (HCMV) protein, that was previously shown to block the MHC class I antigen presentation pathway, has been shown herein to block the MHC class II pathway. This is surprising because the class I and class II proteins are not homologous. US2 caused degradation of class II-alpha proteins and also class II-DM-alpha, part of an enzymatic complex required for loading of antigenic peptides. In this way, US2 has a double inhibitory effect on the MHC class II pathway. US2 expression in cells effectively blocked presentation of antigens to CD4+ T lymphocytes. US2, or soluble variants thereof, can be used to reduce inappropriate immune responses directed to vectors, or expressed transgenes. In addition, such molecules can be used to block immunity to transplanted cells or organs or in autoimmune diseases.