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.
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.
Bieganowska
K
K
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Höllsberg
P
P
Buckle
G J
GJ
Lim
D G
DG
Greten
T F
TF
Schneck
J
J
Altman
J D
JD
Jacobson
S
S
Ledis
S L
SL
Hanchard
B
B
Chin
J
J
Morgan
O
O
Roth
P A
PA
Hafler
D A
DA
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