Identification Of Immunodominant HIV-1-specific CD8+T Cell Epitopes In Chinese

Acquired immunodeficiency syndrome (AIDS) has currently become a serious infectious disease against the health of mankind. Despite the initial success of HAART in controlling HIV-1 replication and dramatically decreasing morbidity and mortality of HIV-1, there are many limitations for this therapeutic approach, including the serious adverse effects of the drugs, emergence of drug-resistant, HIV-1 mutants and poor adherence. Thus the need for a vaccine that protects against HIV-1 infection or attenuates disease has never been more urgent. Large number of studies show that cytotoxic T cells (CTL) response in controlling HIV-1 and SIV replication play an important role. Thus inducing a strong CTL response to HIV-1 vaccine is as a primary consideration.We selected individuals infected with HIV-1 infection and assessed HIV-1-specific CTL responses using overlapping peptides spanning all expressed HIV-1 proteins of clade B and C using a gamma interferon–enzyme-linked immunospot (ELISpot) assay. Furthermore, we identified a number of CTL immunodominant epitope. This study is of critical importance in planning further vaccine design and experimental study in China.The main research contents and results are as follows:1. HIV-1-specific CTL responses in 109 patients infected with HIV-1 were analyzed with ELISpot assay. 382 out of 413 peptides (92.5%) could be recognized by at least one patient. The top four frequently recognized peptides were all from Nef protein. Gag-p24 and Nef were the top two protein subunits which could be targeted most frequently and induced strongest CTL responses. On the contrary, Vpu was the bottom one.2. We divided the subjects into 3 groups: CD4<200/μl, 200/μl400/μl. We found that breadth and magnitude of HIV-1-specific CTL responses in CD4<200/μl group was significantly lower than that in other two groups. In protein subunit level, breadth and magnitude of HIV-1 Gag, Pol and Rev specific CTL responses in CD4>400/μl group was significantly higher than that in CD4<200/μl group(p=0.004 and 0.034; p=0.026 and 0.005; p=0.024 and p=0.025). The decline of Gag-specific CTL responses was due to the drop of CTL responses against two protein subunits (p24 and p15). However, all the 3 protein subunits of Pol took part in the decline of Pol-specific CTL responses. The strongest CTL responses against gp120, Vpr and Vif occurred in 200/μl