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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Epitope Mapping / methods*
  • Epitopes, T-Lymphocyte / analysis*
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Genes, MHC Class I*
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology*
  • HLA-A Antigens / metabolism
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology*
  • HLA-B Antigens / metabolism
  • HeLa Cells
  • Humans
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / immunology
  • Ligands
  • Peptides / chemistry
  • Peptides / immunology*
  • Peptides / metabolism
  • Protein Binding


  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-B Antigens
  • Immunodominant Epitopes
  • Ligands
  • Peptides