An altered peptide ligand antagonizes antigen-specific T cells of patients with human T lymphotropic virus type I-associated neurological disease.
Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurologic disease associated with HTLV-I infection, in which chronically activated, HTLV-I-specific CD8+ CTL have been suggested to be immunopathogenic. In HLA-A2 HAM/TSP patients, CD8+ HTLV-I-specific CTLs recognize an immunodominant peptide of the HTLV-I Tax protein, Tax11-19. We examined the functional outcome on activation of both cloned peripheral blood and cerebrospinal spinal fluid-derived CTL and bulk PBMC from HAM/TSP patients by altered peptide ligands (APL) derived from HTLV-I Tax11-19. In CTL clones generated from PBMC and CSF of HLA-A2 HAM/TSP patients, an APL substituted at position 5 significantly decreased CTL responses when compared with the native peptide. Moreover, these ligands were also shown to inhibit CTL responses to the native peptide in bulk PBMC of HLA-A2 HAM/TSP patients. These data suggest that a modification of an antigenic peptide at the central position can manipulate the T cell responses in bulk PBMC from different individuals with an inflammatory disease. Additionally, these results have implications for the potential use of APL-based immunotherapy in this T cell-mediated CNS disease.
Kubota
R
R
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Soldan
S S
SS
Martin
R
R
Jacobson
S
S
D019943:Amino Acid Substitution / Q000276:immunology; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D016356:Gene Products, tax / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D010446:Peptide Fragments / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D016356:Gene Products, tax; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell