title: T cells recognizing a 11mer influenza peptide complexed to H-2D(b) show promiscuity for peptide length.
abstract: T-cell repertoire is selected according to self peptide-MHC (major histocompatibility complex) complexes in the thymus. Although most peripheral T cells recognize specific pathogen-derived peptides complexed to self-MHC exclusively, some possess cross-reactivity to other self or foreign peptides presented by self-MHC molecules; a phenomenon often termed T-cell receptor (TCR) promiscuity or degeneracy. TCR promiscuity has been attributed to various autoimmune conditions. On the other hand, it is considered a mechanism for a relatively limited TCR repertoire to deal with a potentially much larger antigenic peptide repertoire. Such property has also been utilized to bypass self-tolerance for cancer vaccine development. Although many studies explored such degeneracy for peptide of the same length, few studies reported such properties for peptides of different length. In this study, we finely characterized the CD8(+) T-cell response specific for a 11mer peptide derived from influenza A viral polymerase basic protein 2. The short-term T-cell line, despite possessing highly biased TCR, was able to react with multiple peptides of different length sharing the same core sequence. Out data clearly showed the importance of detailed and quantitative assessments for such T-cell specificity. Our data also emphasize the importance of biochemical demonstration of the naturally presented minimal peptide.
authors.affiliation: T Cell Laboratory, School of Molecular Science, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: Damien
authors.initials: D
authors.lastname: Zanker
authors.affiliation: Department of Microbiology and Immunology, Melbourne University, Parkville, Victoria, Australia.
authors.forename: Kylie
authors.initials: K
authors.lastname: Quinn
authors.affiliation: Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Waithman
authors.affiliation: Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Roleen
authors.initials: R
authors.lastname: Lata
authors.affiliation: Ludwig Institute for Cancer Research, Austin Health, Melbourne, Victoria, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Murphy
authors.affiliation: Department of Microbiology and Immunology, Melbourne University, Parkville, Victoria, Australia.
authors.forename: Nicole Louise
authors.initials: NL
authors.lastname: La Gruta
authors.affiliation: T Cell Laboratory, School of Molecular Science, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D002460:Cell Line; D003429:Cross Reactions; D003546:Cysteine Endopeptidases / Q000235:genetics; D064532:Histocompatibility Antigen H-2D / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism*; D037182:T-Cell Antigen Receptor Specificity; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019496:Cancer Vaccines; D064532:Histocompatibility Antigen H-2D; C057027:PB2 protein, Influenzavirus A; D010446:Peptide Fragments; D014764:Viral Proteins; C071313:LMP-2 protein; D012324:RNA-Dependent RNA Polymerase; D003546:Cysteine Endopeptidases