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J Immunol. 2016 Feb 15;196(4):1480-7. doi: 10.4049/jimmunol.1501721. Epub 2016 Jan 18.

The Length Distribution of Class I-Restricted T Cell Epitopes Is Determined by Both Peptide Supply and MHC Allele-Specific Binding Preference.

Author information

1
Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark;
2
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104;
3
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and.
4
Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, B 1650 HMP Buenos Aires, Argentina.
5
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and bpeters@lji.org.

Abstract

HLA class I-binding predictions are widely used to identify candidate peptide targets of human CD8(+) T cell responses. Many such approaches focus exclusively on a limited range of peptide lengths, typically 9 aa and sometimes 9-10 aa, despite multiple examples of dominant epitopes of other lengths. In this study, we examined whether epitope predictions can be improved by incorporating the natural length distribution of HLA class I ligands. We found that, although different HLA alleles have diverse length-binding preferences, the length profiles of ligands that are naturally presented by these alleles are much more homogeneous. We hypothesized that this is due to a defined length profile of peptides available for HLA binding in the endoplasmic reticulum. Based on this, we created a model of HLA allele-specific ligand length profiles and demonstrate how this model, in combination with HLA-binding predictions, greatly improves comprehensive identification of CD8(+) T cell epitopes.

PMID:
26783342
PMCID:
PMC4744552
DOI:
10.4049/jimmunol.1501721
[Indexed for MEDLINE]
Free PMC Article

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