(SHORT COMMUNICATION) The major ligands presented by MHC class I molecules after natural antigen processing are peptides of eight to ten residues in length, and it is widely accepted that the binding preferences of MHC class I molecules play a dominant role in dictating this classic feature of antigen presentation. In this report, we have reassessed the peptide size specificity of class I human leukocyte antigens (HLAs). By lengthening previously defined T cell epitopes by central amino acid insertion, we demonstrate that the peptide length specificity of some common HLA class I alleles (HLA-B*3501, B*0702 and A*2402) is very broad, and includes peptides of up to 25 residues. These data suggest that the length limitation of naturally processed MHC class I-associated peptides is primarily controlled by peptide availability after antigen processing rather than the binding specificity of MHC class I molecules. Furthermore, the findings provide an explanation for recent reports highlighting that epitopes of >10 amino acids play a minor but significant role in virus-specific immune surveillance by CD8(+) T cells.
Bell, M. J., Burrows, J. M., Brennan, R. M., Miles, J. J., Tellam, J., McCluskey, J., Rossjohn, J., Khanna, R., & Burrows, S. R. (2009). The peptide length specificity of some HLA class I alleles is very broad and includes peptides of up to 25 amino acids in length. Molecular Immunology, 46(8-9), 1911 - 1917. https://doi.org/10.1016/j.molimm.2008.12.003