title: Natural HLA-B*2705 protein ligands with glutamine as anchor motif: implications for HLA-B27 association with spondyloarthropathy.
abstract: The presentation of short viral peptide antigens by human leukocyte antigen (HLA) class I molecules on cell surfaces is a key step in the activation of cytotoxic T lymphocytes, which mediate the killing of pathogen-infected cells or initiate autoimmune tissue damage. HLA-B27 is a well known class I molecule that is used to study both facets of the cellular immune response. Using mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of HLA-B*2705(+) cells, we identified 200 naturally processed HLA-B*2705 ligands. Our analyses revealed that a change in the position (P) 2 anchor motif was detected in the 3% of HLA-B*2705 ligands identified. B*2705 class I molecules were able to bind these six GlnP2 peptides, which showed significant homology to pathogenic bacterial sequences, with a broad range of affinities. One of these ligands was able to bind with distinct conformations to HLA-B27 subtypes differentially associated with ankylosing spondylitis. These conformational differences could be sufficient to initiate autoimmune damage in patients with ankylosing spondylitis-associated subtypes. Therefore, these kinds of peptides (short, with GlnP2, and similar low affinity to all HLA-B27 subtypes tested but with unlike conformations in differentially ankylosing spondylitis-associated subtypes) must not be excluded from future researches involving potential arthritogenic peptides.
authors: Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain.
authors: Susana
authors: S
authors: Infantes
authors: Elena
authors: E
authors: Lorente
authors: Eilon
authors: E
authors: Barnea
authors: Ilan
authors: I
authors: Beer
authors: Alejandro
authors: A
authors: Barriga
authors: Fátima
authors: F
authors: Lasala
authors: Mercedes
authors: M
authors: Jiménez
authors: Arie
authors: A
authors: Admon
authors: Daniel
authors: D
authors: López
mesh_terms: D020816:Amino Acid Motifs; D002460:Cell Line; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D025242:Spondylarthropathies / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: C464936:HLA-B*27:05 antigen; D015796:HLA-B27 Antigen; D010455:Peptides