title: Human endogenous retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods.
abstract: BACKGROUND
  An estimated 10-20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial.
  
  
  RESULTS
  Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets.
  
  
  CONCLUSIONS
  Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.
authors.affiliation: Department of Immunology, University of Toronto, 1 King's College Circle, Rm 6352, Toronto, ON M5S 1A8, Canada. brad.jones@utoronto.ca
authors.forename: R Brad
authors.initials: RB
authors.lastname: Jones
authors.forename: Fabio E
authors.initials: FE
authors.lastname: Leal
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Hasenkrug
authors.forename: Aluisio C
authors.initials: AC
authors.lastname: Segurado
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Mario A
authors.initials: MA
authors.lastname: Ostrowski
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
mesh_terms: D000328:Adult; D020077:Endogenous Retroviruses / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D015490:HTLV-I Infections / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag