title: Short communication an interferon-γ ELISPOT assay with two cytotoxic T cell epitopes derived from HTLV-1 tax region 161-233 discriminates HTLV-1-associated myelopathy/tropical spastic paraparesis patients from asymptomatic HTLV-1 carriers in a Peruvian population.
abstract: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic and progressive disorder caused by the human T-lymphotropic virus type 1 (HTLV-1). In HTLV-1 infection, a strong cytotoxic T cell (CTL) response is mounted against the immunodominant protein Tax. Previous studies carried out by our group reported that increased IFN-γ enzyme-linked immunospot (ELISPOT) responses against the region spanning amino acids 161 to 233 of the Tax protein were associated with HAM/TSP and increased HTLV-1 proviral load (PVL). An exploratory study was conducted on 16 subjects with HAM/TSP, 13 asymptomatic carriers (AC), and 10 HTLV-1-seronegative controls (SC) to map the HAM/TSP-associated CTL epitopes within Tax region 161-233. The PVL of the infected subjects was determined and the specific CTL response was evaluated with a 6-h incubation IFN-γ ELISPOT assay using peripheral blood mononuclear cells (PBMCs) stimulated with 16 individual overlapping peptides covering the Tax region 161-233. Other proinflammatory and Th1/Th2 cytokines were also quantified in the supernatants by a flow cytometry multiplex assay. In addition, a set of human leukocyte antigen (HLA) class I alleles that bind with high affinity to the CTL epitopes of interest was determined using computational tools. Univariate analyses identified an association between ELISPOT responses to two new CTL epitopes, Tax 173-185 and Tax 181-193, and the presence of HAM/TSP as well as an increased PVL. The HLA-A*6801 allele, which is predicted to bind to the Tax 181-193 peptide, was overpresented in the HAM/TSP patients tested.
authors: Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. ivan.best@upch.pe
authors: Ivan
authors: I
authors: Best
authors: Giovanni
authors: G
authors: López
authors: Michael
authors: M
authors: Talledo
authors: Aidan
authors: A
authors: MacNamara
authors: Kristien
authors: K
authors: Verdonck
authors: Elsa
authors: E
authors: González
authors: Martín
authors: M
authors: Tipismana
authors: Becca
authors: B
authors: Asquith
authors: Eduardo
authors: E
authors: Gotuzzo
authors: Guido
authors: G
authors: Vanham
authors: Daniel
authors: D
authors: Clark
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002353:Carrier State / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D016356:Gene Products, tax / Q000737:chemistry* / Q000276:immunology; D015490:HTLV-I Infections / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D010568:Peru; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; D016356:Gene Products, tax; D010455:Peptides; C514970:tax protein, Human T-lymphotrophic virus 1; D007371:Interferon-gamma