title: Ex vivo analysis of human T lymphotropic virus type 1-specific CD4+ cells by use of a major histocompatibility complex class II tetramer composed of a neurological disease-susceptibility allele and its immunodominant peptide.
abstract: HLA-DRB1*0101 is associated with susceptibility to human T lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Here, we used a synthetic tetramer of DRB1*0101 and its epitope peptide to analyze HTLV-1-specific CD4(+) T cells ex vivo. The frequency of tetramer(+)CD4(+) T cells was significantly greater in patients with HAM/TSP than in healthy HTLV-1 carriers (HCs) at a given proviral load and correlated with HTLV-1 tax messenger RNA expression in HCs but not in patients with HAM/TSP. These cells displayed an early to intermediate effector memory phenotype and were preferentially infected by HTLV-1. T cell receptor gene analyses of 2 unrelated DRB1*0101-positive patients with HAM/TSP showed similar Vbeta repertoires and amino acid motifs in complementarity-determining region 3. Our data suggest that efficient clonal expansion of virus-specific CD4(+) T cells in patients with HAM/TSP does not simply reflect higher viral burden but rather reflects a rapid turnover caused by preferential infection and/or in vivo stimulation by major histocompatibility complex-peptide complexes.
authors.affiliation: Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nose
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kubota
authors.forename: Nilufer P
authors.initials: NP
authors.lastname: Seth
authors.forename: Peter K
authors.initials: PK
authors.lastname: Goon
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Shuji
authors.initials: S
authors.lastname: Izumo
authors.forename: Koichiro
authors.initials: K
authors.lastname: Usuku
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ohara
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Osame
authors.forename: Mineki
authors.initials: M
authors.lastname: Saito
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D016355:Genes, pX / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D015486:HTLV-I Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000235:genetics / Q000276:immunology* / Q000821:virology; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D019562:Viral Load
chemical_list: D015234:HLA-A Antigens; D059811:HLA-DRB1 Chains; C487961:HLA-DRB1*01:01 antigen; D015486:HTLV-I Antigens; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell