Modulation of the strength and character of HIV-specific CD8⁺ T cell responses with heteroclitic peptides

Chronic infection with human immunodeficiency virus (HIV) causes HIV-specific CD8⁺ T cell dysfunction and exhaustion. The strong association between non-progression and maintenance of HIV-specific CD8⁺ T cell cytokine production and proliferative capacities suggests that invigorating CD8⁺ T cell immune responses would reduce viremia and slow disease progression. A series of studies have demonstrated that sequence variants of native immunogenic peptides can generate more robust CD8⁺ T cell responses and that stimulation with these ‘heteroclitic’ peptides can steer responses away from the phenotypic and functional attributes of exhaustion acquired during chronic HIV infection. Incorporation of heteroclitic peptide stimulation within therapeutic vaccines could favour induction of more effective cellular antiviral responses, and in combination with ‘shock and kill’ strategies, contribute towards HIV cure.