Bieganowska, K. ; Hollsberg, P. ; Buckle, G. J. ; Lim, D. G. ; Greten, T. F. ; Schneck, J. ; Altman, J. D. ; Jacobson, Steven; Ledis, S. L. ; Hanchard, Barrie; Chin, J. ; Morgan, Owen St.C.; Roth, P. A. ; Hafler, D. A.
Author Affiliation, Ana.
Department of Pathology
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
Journal of Immunology
Date of Publication
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.....