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M9640645.TXT
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1996-03-04
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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).