BACKGROUND: Versatile application of vaccines designed to bring forth CD8⁺ T-cell responses in different racial or ethnic groups will require inclusion of immunodominant T-cell epitopes presented by a variety of class I HLA molecules recognized by a high frequency of individuals.

Methods: To facilitate development of a widely applicable HIV vaccine, this study determined the positive responder frequencies of previously described CD8 T-cell epitopes (n = 48), as well as the frequencies to novel CD8 epitopes (n = 16) derived from African American and Hispanic adolescents in a cohort of racially and ethnically mixed HIV-1 infected individuals (Caucasians, African American, and Hispanics). Subjects were selected from the REACH study of the Adolescent Medicine HIV/AIDS Research Network and from the UAB HIV clinic. From these cohorts, frozen PBMC from volunteers expressing the appropriate HLA were added assessed in an interferon-g ELISpot assay along with the optimal peptides (8-11mers) corresponding to HIV-1 clade B Gag, Pol, Env, Nef, Tat or Vpr, that have been previously HLA-restricted.

RESULTS: Epitopes, KIQNFRVYY (Integrase, A*3002), KETINEEAA (p24, B*4002), TERQANFL (p7, B*4002) and KEKGGLEGL (Nef, B*4002) had a > 75% identity among B clade isolates and had a large number (38%–60%) of individuals responding to them. The HLA-B*57 restricted p24 KAFSPEVIPMF response was present in 6/6 individuals tested and all clade B sequences in the database have this identical epitope. Conversely, 80% of individuals that carried HLA-B40 recognized p24 AEWDRVHPV despite only 14% identity of this sequence with other clade B isolates. In summary, 5/16 novel epitopes were recognized by at least 50% of subjects with the appropriate HLA class I alleles. Similarily, 10/48 of the previously described epitopes had high responder frequencies. Additionally, 12/16 (75%) of the novel peptides identified in our work were recognized by individuals of different racial backgrounds compared with 21/48 (44%) of epitopes identified by others. Notably, some peptides appeared to be preferentially recognized by participants from a particular racial/ethnic group, even when they share similar HLA profiles with participants in another ethnic group.

Conclusions: We have identified a number of highly conserved CTL epitopes that are frequently recognized in persons of diverse racial backgrounds. Such information is relevant to the development of CTL-inducing vaccines for global use.