title: Preferential binding of unusually long peptides to MHC class I and its influence on the selection of target peptides for T cell recognition.
abstract: A classic feature of antigen presentation for CD8+ T cell recognition is that MHC class I molecules generally present peptides of 8-10 amino acids in length. However, recent studies have demonstrated that peptides of >10 residues play a significant role in immune surveillance by T cells restricted by some HLA class I alleles. In the present study, we describe several examples of unusually long viral peptides of 11 or 12 residues, recognized by CTLs in the context of HLA-B35. Interestingly, all these immunogenic peptides completely encompass shorter canonical length sequences that conform to the HLA-B35 binding motif, but which fail to stimulate detectable T cell responses. The mechanism for this phenomenon appears to involve the preferential binding to HLA-B35 of the atypically long CD8+ T cell target peptides over the overlapping canonical length sequences. These data suggest that the peptide length specificity of some HLA class I alleles is broad, allowing peptides of >10 residues to sometimes dominate over canonical length class I ligands as targets for T cell recognition.
authors.affiliation: Queensland Institute of Medical Research and Australian Centre for Vaccine Development, 300 Herston Road, Herston 4029, Brisbane, Australia.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Burrows
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Bell
authors.forename: Rebekah
authors.initials: R
authors.lastname: Brennan
authors.forename: John J
authors.initials: JJ
authors.lastname: Miles
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
authors.forename: Scott R
authors.initials: SR
authors.lastname: Burrows
mesh_terms: D017951:Antigen Presentation; D002460:Cell Line; D015797:HLA-B35 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*
chemical_list: D015797:HLA-B35 Antigen; D015395:Histocompatibility Antigens Class I; D010455:Peptides