PMID- 21453202 OWN - NLM STAT- MEDLINE DCOM- 20120302 LR - 20220129 IS - 1931-8405 (Electronic) IS - 0889-2229 (Linking) VI - 27 IP - 11 DP - 2011 Nov TI - Short communication 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. PG - 1207-12 LID - 10.1089/AID.2011.0029 [doi] AB - 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 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-gamma 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. FAU - Best, Ivan AU - Best I AD - Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. ivan.best@upch.pe FAU - Lopez, Giovanni AU - Lopez G FAU - Talledo, Michael AU - Talledo M FAU - MacNamara, Aidan AU - MacNamara A FAU - Verdonck, Kristien AU - Verdonck K FAU - Gonzalez, Elsa AU - Gonzalez E FAU - Tipismana, Martin AU - Tipismana M FAU - Asquith, Becca AU - Asquith B FAU - Gotuzzo, Eduardo AU - Gotuzzo E FAU - Vanham, Guido AU - Vanham G FAU - Clark, Daniel AU - Clark D LA - eng GR - G0601072/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110509 PL - United States TA - AIDS Res Hum Retroviruses JT - AIDS research and human retroviruses JID - 8709376 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Gene Products, tax) RN - 0 (Peptides) RN - 0 (tax protein, Human T-lymphotrophic virus 1) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Aged MH - Amino Acid Sequence MH - Carrier State/diagnosis/immunology/virology MH - Epitope Mapping MH - Epitopes, T-Lymphocyte/chemistry/*immunology MH - Female MH - Gene Products, tax/*chemistry/immunology MH - HTLV-I Infections/diagnosis/immunology/virology MH - Human T-lymphotropic virus 1/*immunology MH - Humans MH - Interferon-gamma/*analysis MH - Male MH - Middle Aged MH - Molecular Sequence Data MH - Paraparesis, Tropical Spastic/*diagnosis/immunology/virology MH - Peptides/chemistry/*immunology MH - Peru MH - T-Lymphocytes, Cytotoxic/*immunology MH - Young Adult EDAT- 2011/04/02 06:00 MHDA- 2012/03/03 06:00 CRDT- 2011/04/02 06:00 PHST- 2011/04/02 06:00 [entrez] PHST- 2011/04/02 06:00 [pubmed] PHST- 2012/03/03 06:00 [medline] AID - 10.1089/AID.2011.0029 [doi] PST - ppublish SO - AIDS Res Hum Retroviruses. 2011 Nov;27(11):1207-12. doi: 10.1089/AID.2011.0029. Epub 2011 May 9.