Limited T cell receptor usage by HTLV-I tax-specific, HLA class I restricted cytotoxic T lymphocytes from patients with HTLV-I associated neurological disease.
T cell receptor (TCR) V alpha and V beta chain usage of HTLV-I tax-specific, HLA class I restricted CD8+ cytotoxic T cells (CTL) was determined from lymphocytes obtained from peripheral blood of patients with HTLV-I associated neurological disease. To characterize TCR repertoire, CD8+ lymphocytes from peripheral blood were cloned in limiting dilution, and the resulting wells were screened for HTLV-I-specific precursor CTL activity. RNA was isolated from HLA-A2 restricted HTLV-I tax peptide-specific (tax 11-19; LLFGYPVYV) CD8+ CTL lines and cDNA was analyzed by PCR amplification using V alpha and V beta chain family-specific oligonucleotide primers. The results indicate that CD8+ cytotoxic T cell lines from HLA-A2 HAM/TSP patients express a limited repertoire of T cell receptor chains which may correlate with duration and severity of disease. The restricted use of TCR genes expressed by antigen-specific CTL may play a critical role in the pathogenesis of HAM/TSP and may be of value in developing immunotherapeutic strategies that focus on eliminating these cells or inhibiting their activity.
Elovaara
I
I
Department of Neurology, Tampere University Hospital, Finland.
Utz
U
U
Smith
S
S
Jacobson
S
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D016356:Gene Products, tax / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016356:Gene Products, tax; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta