CD8+ T-Cell Epitopes Mapped on the Human Amyloid-Beta Precursor Protein Exhibit Highest Population Coverage in South Korea
Jesther Ryan G. Cinco and Arturo L. Gaitano III* (36-50)
Abstract
Alzheimer’s disease (AD) is the prevalent form of dementia caused by the accumulation of neurotoxic amyloid-beta (Aβ) plaques produced by the cleavage of the human Aβ precursor protein (HAPP). Clearance of Aβ can be promoted via the apoptosis of peripheral cells where HAPP is overexpressed. This can be achieved by the induction of an immune response via exposure to CD8+ T-cell epitopes from HAPP. Immunoinformatics was used to map these epitopes and the human leukocyte antigens (HLAs) that pair with them. Six immunogenic epitopes were obtained, with one epitope exhibiting “promiscuity”,” binding to two different HLAs. A total of seven epitope-HLA pairs were identified with their respective binding free energies and dissociation constants: DTKEGILQY- HLA-A*26:01 (−13.3, 4.20E-10), TPDAVDKY- HLA-B*35:01 (−10.9, 2.10E-08), EVHHQKLVFF- HLA-A*26:01 (−11.1, 1.40E-08), KADKKAVIQHF- HLA-B*58:01 (−10.0, 8.40E-08), AEPQIAMF- HLA-B*44:02 (−9.90, 1.10E-07), AEPQIAMF- HLA-B*44:03 (−8.90, 5.70E-07), and LLPVNGEF- HLA-B*15:01 (−7.00, 1.20E-05). While most of the epitope-HLA pairs exhibited good binding evidenced by their low binding free energies and dissociation constants, AEPQIAMF- HLA-B*44:03 and LLPVNGEF- HLA-B*15:01 did not meet the required threshold. The epitopes are nonallergenic and nontoxic and exhibit significant sequence conservation across different isoforms. They also do not demonstrate significant cross-reactivity with other proteins in the human proteome. The identified epitope-HLA pairs showed highest population coverage in the East Asian region, specifically in South Korea and Japan. These results indicate that these CD8+ T-cell epitopes can be used for potential peptide vaccine candidate especially in the identified regions.