Differential narrow focusing of immunodominant human immunodeficiency virus Gag-specific cytotoxic T-lymphocyte responses in infected African and Caucasoid adults and children

Cytotoxic T-lymphocyte (CTL) activity plays a central role in control of vi ral replication and in determining outcome in cases of human immunodeficien cy virus type 1 (HIV-1) infection. Incorporation of important CTL epitope s equences into candidate vaccines is, therefore, vital. Most CTL studies hav e focused upon small numbers of adult Caucasoid subjects infected with clad e-B virus, whereas the global epidemic is most severe in sub-Saharan Africa n populations and predominantly involves clade-C infection in both adults a nd children. In this study, sensitive enzyme-linked immunospot (elispot) as says have been utilized to identify the dominant Gag-specific CTL epitopes targeted by adults and children infected with clade-B or -C virus, Cohorts evaluated included I 1 B-clade-infected Caucasoid American and African Amer ican adults and children and 37 C-clade-infected African adults and childre n from Durban, South Africa. The results show that 3 out of 46 peptides spa nning p17(Gag) and p24(Gag) sequences tested contain two-thirds of the domi nant Gag-specific epitopes, irrespective of the clade, ethnicity, or age gr oup studied. However; there were distinctive differences between the domina nt responses made by Caucasoids and Africans. Dominant responses in Caucaso ids were more often within p17(Gag) peptide residues 16 to 30 (38 versus 12 %; P < 0.01), while p24(Gag) peptide residues 41 to 60 contained the domina nt Gag epitope more often in the African subjects tested (39 versus 4%; P < 0.005), Within this 20-mer p24(Gag), an epitope presented by both B42 and B81 is defined which represents the dominant Gag response in >30% of the to tal infected population in Durban. This epitope is closely homologous with dominant HIV-2 and simian immunodeficiency virus Gag-specific CTL epitopes. The fine focusing of dominant CTL responses to these few regions of high i mmunogenicity is of significance to vaccine design.