Idely distributed throughout the entire genome, with Gag, Pol and Nef
Idely distributed throughout the entire genome, with Gag, Pol and Nef being the most frequently targeted. Compared to the dominant epitopes scattered within the Gag protein, those in Nef are clustered in the central region of the protein. The subdominant epitopes, targeted by more than 10 but less than 15 of the subjects, are mostly located in p24, Nef, integrase, Vpr and Vif. High cross-recognition of HIV-1 specific CTL responses was observed in this study. When looking at the CTL recognition frequency at the single peptide level, along with the distribution of immunodominant OLPs, the profile of cross-recognition between clade B and C peptides can clearly be seen (Figure 2). To further assess the cross-recognition of CTL responses to clades B and C peptides, thetwo peptide sets were 5-BrdU biological activity classified into the following categories, (i) both B PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26778282 and C peptides not recognized, (ii) both B and C peptides recognized by at least one subject, (iii) only C peptides recognized by at least one subject and (iv) only B peptides recognized by at least one subject. The results are represented with a Venn diagram (Figure 3) and about 22 of the corresponding OLPs (92/413) derived from both the clades B and C proteome are not targeted by CTL. Of the remaining OLPs, more than 68 (219/ 321) can be cross-recognized. We also analyzed the crossrecognition by looking at the total CTL responses detected by clades B and C peptide sets. There are 1352 responses observed when applying clade B OLPs, and 1574 responses to clade C OLPs. Of the responses directed to clade C OLPs, 61.75 (972/1574) PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27532042 can be observed when tested with corresponding clade B OLPs.Correlation of CTL responses with immune control of HIV1 infection Firstly, we examined the correlation of CTL responses with CD4 cell counts and viral loads and found that there are no significant correlations between the overall breadth of responses and the CD4 cell count or plasma viral load. However, a weak negative correlation between the total magnitude and the CD4 cell count was observed (R = 0.260, p = 0.0442 for clade B OLP set; R = -0.283, p = 0.0285 for clade C OLP set, Pearson Correlation test).Page 5 of(page number not for citation purposes)Retrovirology 2007, 4:http://www.retrovirology.com/content/4/1/Figure 2 The immunodominance and cross-reactivity analysis The immunodominance and cross-reactivity analysis. The location of immunodominant and subdominant epitopes in the HIV-1 proteome. Five classes of recognition frequency are represented in the figure, (i) recognition frequency more than 15 , (ii) more than 10 but less than 15 , (iii) more than 5 but less than 10 , (iv) more than 0 but less than 5 and (v) not recognized in the study population. Inserted clade B fragments in the CRF07_BC genome are indicated as red bars adjacent to X-axis. When looking at specific HIV-1 proteins, we found that an increased breadth of CTL responses targeting Gag (especially p24 and p15) resulted in decreased plasma viral load, while for Nef and Vpu, increased breadth or magnitude of CTL responses corresponded to increased plasma viral load. However, these correlates between the breadth of CTL responses to specific proteins and the plasma viral load can only be observed in consensus clade C peptide sets, with the exception of p15. We then classified the subjects into three groups based on their CD4 cell counts and compared the breadth and magnitude of CTL responses. The results show stronger and broader CTL responses.
