P24.10
Background: Increasing evidence suggests that virus-specific CD4 T cells contribute to immune-mediated control of HIV infection. However, the specificities of CD4 T cell responses are poorly defined, particularly in clade C infection. We conducted a comprehensive analysis of virus-specific CD4 T cell responses, defined HLA class II-restriction of detectable responses in clade C infection and compared immunodominant patterns between clade B and clade C CD4 T cell responses.
Methods: Immunodominant hierarchies of HIV-specific CD4 T cell responses were defined using CD8 depleted PBMCs in the IFNγ ELISPOT assay. Host genetic effects of class II HLA-DRB1 alleles on HIV viremia were assessed using the HLA-DRB1 restriction assay. Immunodominant patterns and restriction characteristics of HIV-specific CD4 T cell responses from our clade C study was compared to previously published data on CD4 T cell responses in clade B HIV infection.
Results: Notable differences were identified between the immunodominance hierarchies of HIV-specific CD4 T cell responses in chronic clade C and B infection. In particular, OLP 25(46-62) in the Gag p24 region, one of the dominant epitopes targeted by 33% of responders in clade C infection was not targeted in clade B infection. The OLP 41(164-181) epitope, associated with spontaneous control in clade B was dominant in both clade B and C. Consistent with what has been observed in clade B infection, HLA class II DRB1 restriction in clade C HIV infected individuals showed epitope promiscuity. For example, OLP 163(76-93) was restricted by both HLA-DRB1*13:01 and HLA-DRB1*11:02.
Conclusions: Observed differences in epitope targeting, by HIV-specific CD4 T cell responses, between HIV clade B and C suggests that future vaccines should incorporate immunodominant epitopes targeted by CD4 T cell responses in different clades and ethnicities. Additionally, epitope promiscuity among class II HLA molecules should be taken into account for vaccines designed to induce CD4 T cell responses.
