De Investigaciones Cient icas and Universidad Aut oma, Madrid, Spain and also the �Faculty of Biology, Technion-Israel Institute of Technologies, Haifa 32000, IsraelBackground: Reactive arthritis is an HLA-B27-associated illness triggered by Chlamydia trachomatis. Results: Three chlamydial peptides endogenously presented by mTORC2 Inhibitor Source HLA-B27 were identified. All had been homologous to humanderived sequences, and one showed conformational similarity to a self-derived HLA-B27 ligand. Conclusion: Molecular mimicry amongst chlamydial and self-derived HLA-B27 ligands isn’t uncommon. Significance: Molecular mimicry may possibly contribute towards the pathology of reactive arthritis. Reactive arthritis (ReA) is definitely an HLA-B27-associated spondyloarthropathy that is definitely triggered by diverse bacteria, including Chlamydia trachomatis, a frequent intracellular parasite. HLA-B27-restricted T-cell responses are elicited against this bacterium in ReA individuals, but their pathogenetic significance, autoimmune possible, and relevant epitopes are unknown. Higher resolution and sensitivity mass spectrometry was applied to identify HLA-B27 ligands endogenously processed and presented by HLA-B27 from three chlamydial proteins for which T-cell epitopes have been predicted. Fusion protein constructs of ClpC, Na -translocating NADH-quinone reductase subunit A, and DNA primase have been expressed in HLA-B27 cells, and their HLA-B27-bound peptidomes had been searched for endogenous bacterial ligands. A non-predicted peptide, distinct from the predicted T-cell epitope, was identified from ClpC. A peptide recognized by T-cells in vitro, NQRA(330 38), was detected in the reductase subunit. That is the second HLA-B27-restricted T-cell epitope from C. trachomatis with relevance in ReA Nav1.8 Inhibitor Storage & Stability demonstrated to become processed and presented in live cells. A novel peptide from the DNA primase, DNAP(21123), was also discovered. This was a larger variant of a recognized epitope and was highly homologous to a self-derived natural ligand of HLA-B27. All three bacterial peptides showed higher homology with human sequences containing the binding motif of HLA-B27. Molecular dynamics simulations further showed a striking conformational similarity between DNAP(21123) and its homologous and significantly much more flexible human-derived HLA-B27 ligand. The results recommend that molecular mimicry in between HLA-B27-restricted bacterial and self-derived epitopes is frequent and may well play a part in ReA. Thiswork was supported in element by Plan Nacional de I D i Grants SAF2008/00461 and SAF2011/25681 and Red de Inflamacion y Enfermedades Reumaticas, Instituto de Salud Carlos III, Grant RD08/0075 (to J. A. L. C.); USA-Israel Binational Science Foundation Grant BSF 2009393 (to A. A.); and Comunidad Aut oma de Madrid Grant S2010-BMD-2457BIPEDD2 (to A. M.). 1 A fellow on the Ministry of Education in the Government of Chile. 2 Present address: Whitehead Institute for Biomedical Analysis, Cambridge, MA 021452. three Supported by Strategy Nacional de I D i Grant BFU2011-24595. 4 Supported by the AMAROUTO program (Fundaci Severo Ochoa) and an institutional grant of the Fundaci Ram Areces towards the Centro de Biolog Molecular Severo Ochoa. Present address: Repsol, Technologies Center, M toles, 28045 Madrid, Spain. 5 To whom correspondence must be addressed: Centro de Biolog Molecular Severo Ochoa, c/ Nicol Cabrera N. 1, Universidad Aut oma, 28049 Madrid, Spain. Tel.: 34-91-196-4554; Fax: 34-91-196-4420; E-mail: aldecastro@cbm. uam.es.MHC class I (MHC-I) molecules present endogenous peptides derived fr.