Abstract
BackgroundCD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the different HIV-1 clades distributed world-wide. Unfortunately, little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia.Methodology/Principal FindingsTo identify dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected subjects we drew upon data from an immunological screen of 100 HIV-1 clade CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24, 277YSPVSILDI285, YI9). Over 75% of Cw*0102+ve subjects targeted this epitope, representing the strongest response in more than a third of these individuals. This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57 and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was frequently observed in Cw*0102+ve subjects, suggestive of strong selection pressure being exerted by this common CD8+ T cell response.Conclusions/SignificanceAs HLA-Cw*0102 is frequently expressed in the Thai population (allelic frequency of 16.8%), this immunodominant Cw*0102-restricted Gag epitope may represent an attractive candidate for vaccines specific to CRF01_AE and may help facilitate further studies of immunopathogenesis in this understudied HIV-1 clade.
Highlights
Treatment of HIV-1 infections with antiretroviral therapy has had an enormous impact on delaying disease progression in HIV-1 infections [1]
We have identified a frequently targeted novel immunodominant CD8 epitope in Gag in HIV-1 clade CRF01_AE infected subjects from Thailand
To identify commonly targeted CD8+ T cell epitopes in the Thai population, we drew upon data from an immunological screen of a cohort of 100 treatment naıve, HIV-1 clade CRF01_AE infected subjects (Table 1) using an IFN-c ELISpot assay and overlapping 18-mer peptides spanning the entire HIV-1 clade CRF01_AE genome (Buranapraditkun et al, manuscript in preparation)
Summary
Treatment of HIV-1 infections with antiretroviral therapy has had an enormous impact on delaying disease progression in HIV-1 infections [1]. It is believed that the cellular immune response [4,5,6,7], in addition to neutralizing antibodies, plays a key role in the control of HIV [8,9,10]. Their ability to recognize infected cells depends upon the presentation of viral peptides by host human leukocyte antigen (HLA) molecules on the surface of the cell. Little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia
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