We hypothesize that immune responses to heat shock proteins (HSP) are important in perpetuating and amplifying the immune mediated demyelination occurring in multiple sclerosis (MS). Our hypothesis is based on preliminary data demonstrating increased expression of HSP in brains of patients with MS and increased responses to these proteins in MS spinal fluid T cells. We will investigate these phenomena further by performing the following series of experiments. We propose to: 1. Use a panel of anti-HSP antibodies to determine if patterns of HSP expression are different in MS brains and whether particular cell populations are preferentially stained. 2. Study whether responses to HSP in T cells from the blood and spinal fluids of MS patients differ from those present in fluids from patients with other neurologic diseases (OND). This will be done by determining the antigen specificity of HSP responsive clones from MS and OND patients and by determining their patterns of TCR expression. 3. Determine the patterns of V-beta, V-gamma, and V-delta TCR expression in brains of patients with MS and CSF and compare them to expression patterns of HSP-responsive cells in paired peripheral blood. 4. Use limiting dilution assays to determine the frequency of cells responsive to HSP in the blood of MS and OND patients and study whether changes in such frequencies correlate with changes in the clinical state. 5. Determine the presence of antibodies to HSP in CSF and bloods of MS and OND patients using ELISA and Western blot analyses. The antigen specificities of such antibodies will be determined using recombinant and purified HSP preparations. We will also determine if the oligoclonal bands of Ig present in MS CSF have specificity for HSP.
