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 Tax1 1-19 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 β-chain but not the IL-2R α-chain. Additionally, Tax11-19-reactive CD8⁺ T cells used one predominant TCR Vβ-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-1- associated myelopathy.