title: The peptide length specificity of some HLA class I alleles is very broad and includes peptides of up to 25 amino acids in length.
abstract: 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.
authors.affiliation: Queensland Institute of Medical Research and Australian Centre for Vaccine Development, Herston, Brisbane, Australia.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Bell
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Burrows
authors.forename: Rebekah
authors.initials: R
authors.lastname: Brennan
authors.forename: John J
authors.initials: JJ
authors.lastname: Miles
authors.forename: Judy
authors.initials: J
authors.lastname: Tellam
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
authors.forename: Scott R
authors.initials: SR
authors.lastname: Burrows
mesh_terms: D000595:Amino Acid Sequence / Q000502:physiology*; D001665:Binding Sites / Q000502:physiology; D002478:Cells, Cultured; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D015235:HLA-B Antigens; D010446:Peptide Fragments