       Document 0645
 DOCN  M9640645
 TI    Analysis of the T-cell receptor repertoire of human T-cell leukemia
       virus type 1 (HTLV-1) Tax-specific CD8+ cytotoxic T lymphocytes from
       patients with HTLV-1-associated disease: evidence for oligoclonal
       expansion.
 DT    9604
 AU    Utz U; Banks D; Jacobson S; Biddison WE; Institut de recherches
       cliniques de Montreal, Laboratoire; d'Immunologie, Montreal, Canada.
 SO    J Virol. 1996 Feb;70(2):843-51. Unique Identifier : AIDSLINE
       MED/96135194
 AB    Human T-cell leukemia virus type 1 (HTLV-1)-associated
       myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic,
       progressive neurological disease characterized by marked degeneration of
       the spinal cord and the presence of antibodies against HTLV-1. Patients
       with HAM/TSP, but not asymptomatic carriers, show very high precursor
       frequencies of HTLV-1-specific CD8+ T cells in peripheral blood and
       cerebrospinal fluid, suggestive of a role of these T cells in the
       pathogenesis of the disease. In HLA-A2+ HAM/TSP patients,
       HTLV-1-specific T cells were demonstrated to be directed predominantly
       against one HTLV-1 epitope, namely, Tax11-19. In the present study, we
       analyzed HLA-A2-restricted HTLV-1 Tax11-19-specific cytotoxic T cells
       from three patients with HAM/TSP. An analysis of the T-cell receptor
       (TCR) repertoire of these cells revealed an absence of restricted
       variable (V) region usage. Different combinations of TCR V alpha and V
       beta genes were utilized between, but also within, the individual
       patients for the recognition of Tax11-19. Sequence analysis of the TCR
       showed evidence for an oligoclonal expansion of few founder T cells in
       each patient. Apparent structural motifs were identified for the CDR3
       regions of the TCR beta chains. One T-cell clone could be detected
       within the same patient over a period of 3 years. We suggest that these
       in vivo clonally expanded T cells might play a role in the pathogenesis
       of HAM/TSP and provide information on HTLV-1-specific TCR which may
       elucidate the nature of the T cells that infiltrate the central nervous
       system in HAM/TSP patients.
 DE    Amino Acid Sequence  Base Sequence  Cell Line  Cells, Cultured  Clone
       Cells  DNA Primers  Epitopes/IMMUNOLOGY  Gene Products, tax/*IMMUNOLOGY
       Human  HLA-A2 Antigen  HTLV-I/*IMMUNOLOGY  Male  Middle Age  Molecular
       Sequence Data  Paraparesis, Tropical Spastic/*IMMUNOLOGY  Receptors,
       Antigen, T-Cell, alpha-beta/*IMMUNOLOGY  T-Lymphocytes,
       Cytotoxic/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

