An altered peptide ligand antagonizes antigen-specific T cells of patientswith human T lymphotropic virus type I-associated neurological disease

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical s pastic paraparesis (HAM/TSP) is an inflammatory neurologic disease associat ed with HTLV-I infection, in which chronically activated, HTLV-I-specific C D8(+) CTL have been suggested to be immunopathogenic. In HLA-A2 HAM/TSP pat ients, CD8(+) HTLV-I-specific CTLs recognize an immunodominant peptide of t he HTLV-I Tax protein, Tax(11-19). We examined the functional outcome on ac tivation of both cloned peripheral blood and cerebrospinal spinal fluid-der ived CTL and bulk PBMC from HAM/TSP patients by altered peptide ligands (AP L) derived from HTLV-I Tax(11-19). In CTL clones generated from PBMC and CS F of HLA-A2 HAM/TSP patients, an APL substituted at position 5 significantl y decreased CTL responses when compared with the native peptide. Moreover, these ligands were also shown to inhibit CTL responses to the native peptid e in bulk PBMC of HLA-A2 HAM/TSP patients. These data suggest that a modifi cation of an antigenic peptide at the central position can manipulate the T cell responses in bulk PBMC from different individuals,vith an inflammator y disease. Additionally, these results have implications for the potential use of APL-based immunotherapy in this T cell-mediated CNS disease.