title: Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy.
abstract: Human T cell lymphotropic virus-I (HTLV-I)-associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetramers loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR Vbeta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bieganowska
authors.forename: P
authors.initials: P
authors.lastname: Höllsberg
authors.forename: G J
authors.initials: GJ
authors.lastname: Buckle
authors.forename: D G
authors.initials: DG
authors.lastname: Lim
authors.forename: T F
authors.initials: TF
authors.lastname: Greten
authors.forename: J
authors.initials: J
authors.lastname: Schneck
authors.forename: J D
authors.initials: JD
authors.lastname: Altman
authors.forename: S
authors.initials: S
authors.lastname: Jacobson
authors.forename: S L
authors.initials: SL
authors.lastname: Ledis
authors.forename: B
authors.initials: B
authors.lastname: Hanchard
authors.forename: J
authors.initials: J
authors.lastname: Chin
authors.forename: O
authors.initials: O
authors.lastname: Morgan
authors.forename: P A
authors.initials: PA
authors.lastname: Roth
authors.forename: D A
authors.initials: DA
authors.lastname: Hafler
mesh_terms: D000328:Adult; D018122:B7-1 Antigen / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D016356:Gene Products, tax / Q000737:chemistry* / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000737:chemistry*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology*; D010641:Phenotype; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D019707:Receptors, Chemokine / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012995:Solubility