Induction of CD4+, human T lymphotropic virus type-1-specific cytotoxic T lymphocytes from patients with HAM/TSP. Recognition of an immunogenic region of the gp46 envelope glycoprotein of human T lymphotropic virus type-1.
Although the humoral response to human T lymphotropic virus type-1 (HTLV-I) has been well characterized in patients with HTLV-I-associated neurologic disease (HAM/TSP), little is known about a functional HTLV-I-specific human T cell response, such as CTL, in these patients. To define both the phenotype of the responding CTL and the fine specificity of this response, long term T cell lines were generated from two HAM/TSP patients who were from two different countries. Patient's peripheral blood lymphocytes were repeatedly stimulated in vitro with an HTLV-I expressing autologous T cell line. The resultant long term T cell culture was shown to be CD4+ and cytotoxic for targets expressing HTLV-I Ag. Using a panel of synthetic peptides that span hydrophilic regions of the HTLV-I gp46 envelope glycoprotein, the CTL lines generated from both patients were shown to recognize the same region of the HTLV-I envelope between amino acids 196-209 as defined by the synthetic peptide sp4a1. Interestingly, this sequence overlaps a region of HTLV-I envelope that had also been shown to elicit a strong B cell response in HAM/TSP patients (amino acids 190-203). One CTL line recognized this HTLV-I epitope in the context of HLA DQ5 whereas the other CTL line was restricted by HLA DRw16. The generation of two independent CTL lines from two HAM/TSP patients from different geographic areas that recognize the same region of the HTLV-I envelope glycoprotein highlights the immunogenic nature of this envelope region.
Jacobson
S
S
Neuroimmunology Branch, National Institutes of Health, National Institute of Neurologic Disease and Stroke, Bethesda, MD 20892.
Reuben
J S
JS
Streilein
R D
RD
Palker
T J
TJ
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000032:analysis; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003105:Colombia; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env; D006681:HLA-D Antigens / Q000502:physiology; D006205:Haiti; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D000939:Epitopes; D015686:Gene Products, env; D006681:HLA-D Antigens; D010446:Peptide Fragments; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C055266:gp46 protein, Human T-cell leukemia virus type I