IMMUNOBIOLOGY Degenerate specificity of HTLV-1–specific CD8 T cells during viral replication in patients with HTLV-1–associated myelopathy (HAM/TSP)

1)–associated myelopathy/tropical spas-tic paraparesis (HAM/TSP) is an inflamma-tory neurologic disease caused by HTLV-1 infection, in which HTLV-1–infected CD4 T cells and HTLV-1–specific CD8 T cells may play a role in the disease pathogene-sis. Patients with HAM/TSP have high proviral loads despite vigorous virus-specific CD8 T-cell responses; however, it is unknown whether the T cells are efficient in eliminating the virus in vivo. To define the dynamics of HTLV-1–spe-cific CD8 T-cell responses, we investi-gated longitudinal alterations in HTLV-1 proviral load, amino acid changes in an immunodominant viral epitope, frequency of HTLV-1–specific T cells, and degen-eracy of T-cell recognition in patients with HAM/TSP. We showed that the frequency and the degeneracy of the HTLV-1–spe-cific CD8 T cells correlated well with proviral load in the longitudinal study. The proviral load was much higher in a patient with low degeneracy of HTLV-1– specific T cells compared to that in a patient with comparable frequency but higher degeneracy of the T cells. Further-more, in a larger number of patients di-vided into 2 groups by the proviral load, those with high proviral load had lower degeneracy of T-cell recognition than those with low proviral load. Sequencing analysis revealed that epitope mutations were remarkably increased in a patient when the frequency and the degeneracy were at the lowest. These data suggest that HTLV-1–specific CD8 T cells with degenerate specificity are increased dur-ing viral replication and control the viral infection. (Blood. 2003;101:3074-3081) © 2003 by The American Society of Hematolog