Accumulated evidence points to cytotoxic T-lymphocyte (CTL) recognition of HTLV-I-infected neuronal cells as a pathogenic mechanism in HAM-TSP. However, neuronal cells normally do not express detectable levels of class I or class II MHC molecules, which are required for presentation of antigen to T cells. In an effort to resolve this paradox, we have demonstrated that HTLV-I infection of human neuroblastoma cell lines (HNCL), as a model of neuronal cells, resulted in the expression of HLA-class I and class II (DR, DP, and DQ) molecules, and that class II expression was dependent upon HTLV-I infection. Studies over the past year have further characterized HTLV-I-induced class II expression on the HNCL at the cellular and molecular levels. The major findings are as follows: 1) HTLV-I-infected neuroblastomas expressing HLA-class II molecules can be recognized by superantigen-specific, class II-dependent CTL lines, demonstrating that class II is functionally expressed on the HNCL; 2) binding of proteins to the X2 box of the HLA-DRA promoter correlates with class II expression in the HTLV-I-infected HNCL, and may represent a complex of transacting factors induced by infection that results in class II expression; 3) stable transfectants of HNCL have been generated using a construct that contains the HTLV-I Tax gene under the control of the metallothionein promoter, allowing controlled expression of Tax. Expression of Tax in the HNCL results in HLA-DRA expression, but not class I expression, demonstrating that a viral gene is, at least in part, responsible for HLA-class II induction in the HNCL.
