Heteroclitic human immunodeficiency virus peptides enhance HIV-specific CD8⁺ T cell proliferation and reduce PD-1 expression

Adegoke, Adeolu O. (2015) Heteroclitic human immunodeficiency virus peptides enhance HIV-specific CD8⁺ T cell proliferation and reduce PD-1 expression. Masters thesis, Memorial University of Newfoundland.

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Abstract

Heteroclitic peptides are sequence variants of native peptide epitopes that stimulate T cell responses superior to the native epitope. Since heteroclitic peptides enhance HIVspecific CD8⁺ T cell cytokine production, we investigated whether they reduce signs of HIV-specific CD8⁺ T cell exhaustion. Twenty-four variant peptides were generated from reference human histocompatibility-linked leukocyte antigen (HLA)-A2- restricted peptide epitopes Nef 8391, Nef 135143, Gag 433440 and Gag 7785 with conservative and semi-conservative amino acid substitutions at positions 3, 5 and 7 or 3, 5 and 8 of Gag 433440. Variants that enhanced interferon-gamma (IFN-γ) and/or interleukin-2 (IL-2) production were tested for their effects on proliferation and programmed death-1 (PD-1) expression. Heteroclitic variants enhanced HIV-specific CD8⁺ T cell proliferation by > 20% in 13/29 cases, induced lower PD-1 expression by 15% - 50% in 10 cases, and by ≥ 50% in 3 cases. These data indicate unique immunotherapeutic potential for heteroclitic peptides.

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