An interferon-gamma 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

I Best, G López, M Talledo, A MacNamara, K Verdonck, E González, M Tipismana, B Asquith, E Gotuzzo, G Vanham, D Clark

    Research output: Contribution to journalA1: Web of Science-article

    1 Downloads (Pure)

    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-gamma enzyme-linked immunospot (ELISPOT) responses against the region spanning aminoacids 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-gamma ELISPOT assay using peripheral blood mononuclear cells (PBMC) stimulated with 16 individual overlapping peptides covering the Tax region 161-233. Other pro-inflammatory 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 <i>HLA-A*6801</i>, which is predicted to bind to Tax 181-193 peptide, was over-presented in the HAM/TSP patients tested.
    Original languageEnglish
    JournalAIDS Research and Human Retroviruses
    Volume27
    Issue number11
    Pages (from-to)1207-1212
    Number of pages6
    ISSN0889-2229
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Viral diseases
    • HTLV-1
    • Human T lymphotropic virus-type 1
    • Tropical spastic paraparesis
    • Myelopathy
    • Cytotoxicity
    • T-cells
    • Proteins
    • Epitopes
    • Assays
    • ELISPOT
    • Enzyme linked immunosorbent spot
    • Peptides
    • Asymptomatic
    • Taxes
    • Sequencing
    • Peru
    • America-Latin

    Fingerprint

    Dive into the research topics of 'An interferon-gamma 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'. Together they form a unique fingerprint.

    Cite this