HLA class II molecules are required for the presentation of antigen to CD4+ T cells in the induction of immune reactivity and for target recognition by effector T-lymphocytes. Aberrant expression of class II genes has been postulated as a factor in the generation of organ-specific autoimmune disease. While not normally expressed on certain cell types in the central nervous system (CNS), class II can be induced on many of these same cells by various cytokines or infection with viruses. The purpose of this project is to understand molecular genetic mechanisms that control the expression of HLA class II genes in the CNS. Studies over the past year have examined three of these systems: 1) identification of class II gene-enhancer elements that are required for suppression of class II expression in a glioblastoma cell line by interleukin-1beta (IL-1beta); 2) the up-regulation of class II expression on normal human cerebral microvessel endothelial cells by interferon- gamma; and 3) the induction of class II expression on human neuroblastomas by infection with HTLV-I. The major findings are as follows: 1) Evidence has been obtained that indicates the DRalpha gene requires the X box, in addition to the Y box, for a negative response to IL-1beta. 2) Human cerebral microvessel endothelial cells express HLA- class II in response to IFN-gamma treatment. 3) The infection of human neuroblastomas with HTLV-I cocultured with a chronically infected T-cell line, results in the induction of class II transcripts and cell surface class II expression (HLA-DR, -DQ, and -DP).
