Target epitopes of HTLV-1 recognized by class I MHC-restricted cytotoxic T lymphocytes in patients with myelopathy and spastic paraparesis and infected patients with autoimmune disorders

J Med Virol. 2011 Mar;83(3):501-9. doi: 10.1002/jmv.21985.

Abstract

Human T-cell lymphotropic virus type I (HTLV-1) causes adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The different patterns of clinical diseases are thought to be linked to immunogenetic host factors. A variety of autoimmune diseases, such as Sjögren's syndrome, have been reported in persons infected with HTLV-1, although the precise relationship between these disorders and HTLV-1 infection remains unknown. There is no report on the repertoire of HTLV-1-specific CD8+ T-cells in HAM/TSP patients or carriers with autoimmune diseases, both characterized by an abnormal immune state. In this study, to characterize HTLV-1-specific CD8+ T-cells in asymptomatic HTLV-1 carriers, HAM/TSP patients and carriers with autoimmune diseases, we examined the frequency and diversity of HTLV-1-specific CD8+ T-cells using HTLV-1 tetramers. HTLV-1 Env-specific CD8+ T-cells were significantly more frequent in HAM/TSP and carriers with autoimmune diseases compared with asymptomatic HTLV-1 carriers, while the frequency of HTLV-1 Tax-specific CD8+ T-cells was not significantly different among them. CD8+ cells binding to HTLV-1 Tax tetramers in carriers with autoimmune diseases were significantly reduced compared with HAM/TSP patients. This study demonstrates the importance of CD8+ T-cells recognizing HTLV-1 Env-tetramers in HAM/TSP patients and carriers with autoimmune diseases, thereby suggesting that the diversity, frequency and repertoire of HTLV-1 Env-specific CD8+ T-cell clones may be related to the hyperimmune response in HAM/TSP and carriers with autoimmune diseases, although different immunological mechanisms may mediate the hyperimmunity in these conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases / immunology*
  • Epitopes* / immunology
  • Epitopes* / metabolism
  • Gene Products, tax / immunology
  • Gene Products, tax / metabolism
  • Genetic Variation
  • HLA-A Antigens / chemistry
  • HLA-A Antigens / immunology
  • HLA-A Antigens / metabolism
  • Histocompatibility Testing
  • Human T-lymphotropic virus 1 / immunology*
  • Human T-lymphotropic virus 1 / metabolism*
  • Humans
  • Middle Aged
  • Paraparesis, Tropical Spastic / immunology*
  • Protein Binding
  • T-Lymphocytes, Cytotoxic* / immunology
  • T-Lymphocytes, Cytotoxic* / metabolism
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Young Adult

Substances

  • Epitopes
  • Gene Products, tax
  • HLA-A Antigens
  • Viral Envelope Proteins
  • tax protein, Human T-lymphotrophic virus 1