TCR contact residue hydrophobicity is a hallmark of immunogenic CD8 + T cell epitopes
Open accessAbstract
Significance: The design of effective T-cell vaccines against pathogens and tumor antigens is challenged by the highly inefficient identification of the subset of peptides from a given antigen that effectively stimulate an immune response. Here we report that the relative hydrophobicity of T-cell receptor contact residues is markedly enriched in immunogenic major histocompatibility complex class I epitopes in both human and murine MHCs, and in both self and pathogen-derived immunogenic epitopes. Incorporating hydrophobicity into T-cell epitope prediction models increases the efficiency of epitope identification, which will manifest in the time and cost of T-cell vaccine development. Amino acid hydrophobicity may represent a biochemical basis by which T cells discriminate immunogenic epitopes within the background of self peptides.
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The greater hydrophobicity of bacterial peptides might make them preferable for antigen presentation and T cell recognition.
“a property that might make these peptides preferable for antigen presentation16 and recognition by T cells17”
From Identification of bacteria-derived HLA-bound peptides in melanoma (2021) · cites this paper as [17]
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- Authors
- Chowell, D., Krishna, S., Becker, P. D., Cocita, C., Shu, J., Tan, X., Greenberg, P. D., Klavinskis, L. S., Blattman, J. N., & Anderson, K. S.
- Affiliations
- Simon A. Levin Mathematical, Computational, and Modeling Sciences Center,
- Arizona State University (US)
- King's College London (GB)
- University of Washington (US)
- Center for Personalized Diagnostics, and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-03-23
- Volume
- 112
- Issue
- 14
- Pages
- E1754-62
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4394253
- OpenAlex
- W1997011259
- Cited by
- 239
- References
- 45
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 32 · 2023: 30 · 2022: 34 · 2021: 24 · 2020: 25 · 2019: 20 · 2018: 18 · 2017: 11 · 2016: 8 · 2015: 3
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Cancer Institute (R37CA033084, CA-33084, CA18029, R01CA033084, P01CA018029)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- hydrophobicity, immunogenic epitopes, CD8+ T cells, MHC class I peptides, epitope prediction, artificial neural networks, HIV-1 Gag protein, immunodominance
- MeSH terms
- Adenoviridae, Algorithms, Amino Acids, Animals, Humans, Major Histocompatibility Complex, Mice, Inbred C57BL, Probability, Protein Binding, Receptors, Antigen, T-Cell, Antigen Presentation, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Mice, gag Gene Products, Human Immunodeficiency Virus, Hydrophobic and Hydrophilic Interactions
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