PMID- 23430249 OWN - NLM STAT- MEDLINE DCOM- 20130607 LR - 20211021 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 288 IP - 15 DP - 2013 Apr 12 TI - Natural HLA-B*2705 protein ligands with glutamine as anchor motif: implications for HLA-B27 association with spondyloarthropathy. PG - 10882-9 LID - 10.1074/jbc.M113.455352 [doi] AB - 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. FAU - Infantes, Susana AU - Infantes S AD - Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain. FAU - Lorente, Elena AU - Lorente E FAU - Barnea, Eilon AU - Barnea E FAU - Beer, Ilan AU - Beer I FAU - Barriga, Alejandro AU - Barriga A FAU - Lasala, Fatima AU - Lasala F FAU - Jimenez, Mercedes AU - Jimenez M FAU - Admon, Arie AU - Admon A FAU - Lopez, Daniel AU - Lopez D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130219 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (HLA-B*27:05 antigen) RN - 0 (HLA-B27 Antigen) RN - 0 (Peptides) SB - IM MH - Amino Acid Motifs MH - Cell Line MH - HLA-B27 Antigen/genetics/*immunology/metabolism MH - Humans MH - Peptides/genetics/*immunology/metabolism MH - Protein Binding/genetics/immunology MH - Spondylarthropathies/genetics/*immunology/metabolism/pathology PMC - PMC3624468 EDAT- 2013/02/23 06:00 MHDA- 2013/06/08 06:00 PMCR- 2014/04/12 CRDT- 2013/02/23 06:00 PHST- 2013/02/23 06:00 [entrez] PHST- 2013/02/23 06:00 [pubmed] PHST- 2013/06/08 06:00 [medline] PHST- 2014/04/12 00:00 [pmc-release] AID - S0021-9258(20)67310-0 [pii] AID - M113.455352 [pii] AID - 10.1074/jbc.M113.455352 [doi] PST - ppublish SO - J Biol Chem. 2013 Apr 12;288(15):10882-9. doi: 10.1074/jbc.M113.455352. Epub 2013 Feb 19.