HLA-A24-restricted HTLV-I-specific CTL response reduces the HTLV-I proviral load but the HLA increases the risk of HAM/TSP
- 689 Downloads
KeywordsInfectious Disease Cancer Research Allele Frequency Viral Protein Maximum Response
It is controversial whether HTLV-I-specific CTLs are beneficial or harmful to the host in the development of HAM/TSP. HLA-A2 reduces the risk of HAM/TSP and HLA-A2-restricted HTLV-I Tax11-19-specific CTL response reduces HTLV-I proviral load in asymptomatic HTLV-I carriers (ACs), suggesting that HLA-A2-restricted CTLs are beneficial to the host. Recently, HTLV-I Tax301-309 is newly identified as an immunodominant epitope restricted to HLA-A24 and frequency of Tax301-309-specific CTLs is high in HTLV-I-infected individuals. We investigated whether HLA-A24 also reduces the risk of HAM/TSP and compared the differences between HLA-A2- and HLA-A24-restricted Tax-specific CTL responses. We found that the allele frequency of HLA-A24 was significantly increased in HAM/TSP patients compared to ACs. The frequency of HTLV-I Tax301-309-specific CTLs was higher in HAM/TSP patients than that in ACs and negatively correlated with the HTLV-I proviral load in both HAM/TSP patients and ACs. In the comparison between HLA-A2/Tax11-19-specific CTLs and HLA-A24/Tax301-309-specific CTLs, the maximum responses by antigen stimulation were not different in IFN-gamma and MIP-1beta productions and CD107a expression, however, the functional avidity of the CTLs was 50-fold stronger in Tax301-309-specific CTLs than in Tax11-19-specific CTLs. This suggests that Tax301-309-specific CTLs more efficiently recognize HTLV-I-infected cells when the cells express low levels of viral proteins. Our data suggest that HLA-A24 increases the risk of HAM/TSP and that Tax301-309-specific CTLs may play a role in the pathogenesis of HAM/TSP even though they reduce the proviral load, or other factors related to HLA-A24 may affect the risk.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.