title: Purification and characterization of endogenous peptides extracted from HLA-DR isolated from the spleen of a patient with rheumatoid arthritis.
abstract: We have purified HLA-DR from the spleen of a patient with rheumatoid arthritis. The patient had Felty's syndrome and was heterozygous for the DR4Dw4 antigen. We have isolated endogenous peptides from purified HLA-DR molecules. The peptides were purified by reverse phase HPLC and the major peaks were subjected to N-terminal sequencing. The peptides were derived from a variety of proteins: human serum albumin, human erythroid protein 4.1, 60S ribosomal proteins L31 and L35, VCAM-1, human immunoglobulin lambda chain and cathepsin-S. A peptide corresponding to the sequence of human serum albumin (HSA) residues 106-120 was synthesized and shown to bind to HLA-DR4Dw4 (IC50 = 1.41 microM). We have confirmed and refined current ideas about the structural motif for the binding of peptides to HLA-DR and HLA-DR4Dw4.
authors.affiliation: ZENECA Pharmaceuticals, Mereside, Alderley Park, Macclesfield, GB.
authors.forename: R D
authors.initials: RD
authors.lastname: Gordon
authors.forename: J A
authors.initials: JA
authors.lastname: Young
authors.forename: S
authors.initials: S
authors.lastname: Rayner
authors.forename: R W
authors.initials: RW
authors.lastname: Luke
authors.forename: M L
authors.initials: ML
authors.lastname: Crowther
authors.forename: P
authors.initials: P
authors.lastname: Wordsworth
authors.forename: J
authors.initials: J
authors.lastname: Bell
authors.forename: G
authors.initials: G
authors.lastname: Hassall
authors.forename: J
authors.initials: J
authors.lastname: Evans
authors.forename: S A
authors.initials: SA
authors.lastname: Hinchliffe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology / Q000302:isolation & purification*; D001327:Autoimmune Diseases / Q000276:immunology*; D002403:Cathepsins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003598:Cytoskeletal Proteins; D000939:Epitopes / Q000276:immunology / Q000302:isolation & purification*; D005822:Genetic Vectors; D006681:HLA-D Antigens / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D009479:Neuropeptides; D017924:Nucleopolyhedroviruses / Q000235:genetics; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000302:isolation & purification*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012269:Ribosomal Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012709:Serum Albumin / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D013154:Spleen / Q000737:chemistry*; D018411:Spodoptera / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D001324:Autoantigens; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D000939:Epitopes; D006681:HLA-D Antigens; C053495:HLA-Dw4 antigen; D007146:Immunoglobulin lambda-Chains; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; C489281:RPL35A protein, human; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; D012709:Serum Albumin; D019010:Vascular Cell Adhesion Molecule-1; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; C050985:ribosomal protein L31; D002403:Cathepsins; C028217:cathepsin S