The difference NEF and GAG-SPECIFIC CD8+T lymphocyte responses in control of HIV-1 infectiob in Thaipatients

Abstract

CD8⁺ T lymphocytes are believed to play an important role in the control of Human Immunodeficiency Virus (HIV) infection. Recent studies showed that specificities of CD8⁺ T lymphocytes might have an effect on efficiency of protective immune response. We therefore screened HIV-1-specific CD8⁺ T lymphocytes in 35 HIV-1-seropositive Thais with different level of HIV RNA and in 11 high risk HIV-1-seronegative Thais and their HIV-1-seropositive partners using of Nef and Gag peptides based gamma interferon-enzyme-linked immunospot (ELISpot) assay. In addition, we analysed the amino acid sequences of relevant HIV proteins in non-responsive subjects to study HIV escape mutation. The results demonstrated that the most frequently recognised peptides and the strongest responses were located in Nef, followed by p24 Gag, p17 Gag, and p2p7p1p6 Gag, respectively. There are 30 subjects (85.7%) responded against Nef protein and there are 16 subjects (45.7%) responded against Gag protein. However, neither the breadth nor the magnitude of HIV-1-specific CD8⁺ T lymphocyte responses correlated with plasma viral load. In subgroup analysis, there was no significant difference of responses among individuals with different HIV RNA load. In subjects whose the responses could not be detected had amino acid mutations either within epitope or in the flanking region. However, in case of the discordant couples, we found the different antigenicity recognition against Nef protein. One high risk HIV-1-seronegative subject had vigorous responses against Nef 7, Nef 8, and Nef 9 whilst their partner responded against Nef 9, Nef 14, and Nef 15. These results may indicate that the CD8⁺ T cells specific for Nef 7 and Nef 8 peptides play a critical role in control of HIV-1 infection.