High degree of inter-clade cross-reactivity of HIV-1-specific T cell responses at the single peptide level

Objectives: To determine HIV-1-specific T cell responses in clade B infected individuals recognizing the clade A, Band C consensus sequences in order to assess the degree of inter-clade cross-reactivity of these immune responses at the single epitope level. Methods: HIV-1-specific T cell responses were assessed cross-sectionally in 27 chronically HIV-1-infected individuals from a population infected mainly with clade B viral strains, using an interferon-gamma Elispot assay with a total of 1230 overlapping peptides spanning the entire amino acid sequence of the clade A, B and C 2001 consensus sequences. Results: No significant difference was observed between the total magnitude or breadth of T cell responses recognizing either the clade A, B or C consensus sequences. However, at the single peptide level, 194 T cell responses were identified that recognized only one of the three different clade-specific peptide variants (A : B : C, 34 : 105 : 55), 125 T cell responses recognized two of the three peptide variants (AB : AC : BC, 71 : 15 : 39) and 166 T cell responses (34%) were cross-reactive with all three different peptide variants. Peptides recognized in all three consensus sequence variants had a significantly lower entropy (P < 0.0001) and a significantly higher inter-clade homology (P < 0.0001). Conclusions: Viral epitopes within regions of low HIV-1 clade B diversity and high inter-clade homology can be recognized in the clade A, B and C variants and indicate a wide degree of cross-isolate and cross-clade recognition by HIV-1-specific T cells. These regions may therefore be of particular relevance for the design of HIV-1 vaccines. (c) 2005 Lippincott Williams & Wilkins.