PMID- 27601175 OWN - NLM STAT- MEDLINE DCOM- 20170605 LR - 20181113 IS - 1875-8355 (Electronic) IS - 1572-3887 (Linking) VI - 35 IP - 5 DP - 2016 Oct TI - Multi-modal Binding of a 'Self' Peptide by HLA-B*27:04 and B*27:05 Allelic Variants, but not B*27:09 or B*27:06 Variants: Fresh Support for Some Theories Explaining Differential Disease Association. PG - 346-353 AB - A self-derived-peptide with the same amino acid sequence (N-RRYLENGKETLQR-C) as residues 169-181 of the human leukocyte antigen (HLA) B27 heavy chain is known to bind to MHC Class I complexes containing the HLA-B27 heavy chain. This observation has been invoked previously in at least two different (but related) molecular explanations for the disease-association of the HLA-B27 allele. Here, we use a combination of fluorescence polarization, competitive inhibition and gel filtration chromatographic studies to show that a fluorescently-labeled peptide of the above sequence binds to two disease-associated subtypes of HLA-B27 (namely HLA-B*27:04 and HLA-B*27:05) but not to non-disease-associated subtypes (HLA-B*27:06 or HLA-B*27:09). This differential binding behavior is seen both in (a) peptide binding to complexes of heavy chain (HLA-B27) and light chain (beta(2) microglobulin), and in (b) peptide binding to beta(2) microglobulin-free heavy chains in the aggregated state. Such subtype-specific differences are not seen with two other control peptides known to bind to HLA-B27. Our results support the likelihood of differential peptide binding holding at least one of the keys to HLA-B27's disease association. FAU - Rana, Manish Kumar AU - Rana MK AD - Department of Immunopathology, Research Block A, Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, 160012, India. FAU - Luthra-Guptasarma, Manni AU - Luthra-Guptasarma M AD - Department of Immunopathology, Research Block A, Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, 160012, India. mguptasarma@yahoo.com. LA - eng PT - Journal Article PL - Netherlands TA - Protein J JT - The protein journal JID - 101212092 RN - 0 (Fluorescent Dyes) RN - 0 (HLA-B*27:04 antigen) RN - 0 (HLA-B*27:05 antigen) RN - 0 (HLA-B*27:06 antigen) RN - 0 (HLA-B*27:09 antigen) RN - 0 (HLA-B27 Antigen) RN - 0 (Peptides) RN - 0 (Recombinant Proteins) RN - 38183-12-9 (Fluorescamine) SB - IM MH - Alleles MH - Amino Acid Sequence MH - Autoimmunity MH - Fluorescamine/chemistry MH - Fluorescent Dyes/chemistry MH - Gene Expression MH - HLA-B27 Antigen/*chemistry/genetics/immunology MH - Humans MH - *Models, Immunological MH - Models, Molecular MH - Peptides/*chemistry/genetics/immunology MH - Protein Binding MH - Recombinant Proteins/chemistry/genetics/immunology MH - Staining and Labeling/methods OTO - NOTNLM OT - Disease association OT - Fluorescence polarization OT - Gel filtration OT - Human leukocyte antigen OT - Peptide binding EDAT- 2016/11/04 06:00 MHDA- 2017/06/06 06:00 CRDT- 2016/09/08 06:00 PHST- 2016/11/04 06:00 [pubmed] PHST- 2017/06/06 06:00 [medline] PHST- 2016/09/08 06:00 [entrez] AID - 10.1007/s10930-016-9678-6 [pii] AID - 10.1007/s10930-016-9678-6 [doi] PST - ppublish SO - Protein J. 2016 Oct;35(5):346-353. doi: 10.1007/s10930-016-9678-6.