title: A Comparative Analysis of the Peptide Repertoires of HLA-DR Molecules Differentially Associated With Rheumatoid Arthritis.
abstract: To evaluate similarity of the peptide repertoires bound to HLA-DR molecules that are differentially associated with rheumatoid arthritis (RA), and to define structural features of the shared peptides.
  
  
  
  Peptide pools bound to HLA-DRB1*01:01, HLA-DRB1*04:01, and HLA-DRB1*10:01 (RA associated) and those bound to HLA-DRB1*15:01 (non-RA-associated) were purified and analyzed by liquid chromatography (LC) matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MS) and LC-ion-trap MS. Peptide pools from each allotype were compared in terms of size, protein origin, composition, and affinity (both theoretical and experimental with some peptides). Finally, 1 peptide sequenced from DR1, DR4, and DR10, but not from DR15, was modeled in complex with all 4 HLA-DRB1 molecules and HLA-DRB5*01:01.
  
  
  
  A total of 6,309 masses and 962 unique peptide sequences were compared. DR10 shared 29 peptides with DR1, 9 with DR4, and 1 with DR15; DR1 shared 6 peptides with DR4 and 9 with DR15; and DR4 and DR15 shared 4 peptides. The direct identification of peptide ligands indicated that DR1 and DR10 were the most similar molecules regarding the peptides that they could share. The peptides common to these molecules contained a high proportion of Leu at P4 and basic residues at P8 binding core positions.
  
  
  
  The degree of overlap between peptide repertoires associated with different HLA-DR molecules is low. The repertoires associated with DR1 and DR10 have the highest similarity among the molecules analyzed (∼10% overlap). Among the peptides shared between DR1 and DR10, a high proportion contained Leu(4) and basic residues at the P8 position of the binding core.
authors.affiliation: Institut de Biotecnologia i de Biomedicina and Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Erika
authors.initials: E
authors.lastname: Scholz
authors.affiliation: Institut de Biotecnologia i de Biomedicina and Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Mestre-Ferrer
authors.affiliation: Institut de Biotecnologia i de Biomedicina and Universitat Autònoma de Barcelona, Bellaterra, Spain, and Catalan Institution for Research and Advanced Studies, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Daura
authors.affiliation: InnovativeHealth Group-Parque Científico de Madrid, Madrid, Spain.
authors.forename: Noel
authors.initials: N
authors.lastname: García-Medel
authors.affiliation: CSIC/UAB Proteomics Laboratory, IIBB-CSIC/Institut d'Investigacions Biomèdiques August Pi i Sunyer, Bellaterra, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Carrascal
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Washington.
authors.forename: Eddie A
authors.initials: EA
authors.lastname: James
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Washington.
authors.forename: William W
authors.initials: WW
authors.lastname: Kwok
authors.affiliation: Vall d'Hebron University Hospital Research Institute Proteomics Laboratory, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Canals
authors.affiliation: Institut de Biotecnologia i de Biomedicina and Universitat Autònoma de Barcelona, Bellaterra, Spain. Inaki.Alvarez@uab.es.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Álvarez
mesh_terms: D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002853:Chromatography, Liquid; D059810:HLA-DR Serological Subtypes / Q000378:metabolism; D015798:HLA-DR1 Antigen / Q000378:metabolism; D015804:HLA-DR4 Antigen / Q000378:metabolism; D059811:HLA-DRB1 Chains / Q000378:metabolism*; D059847:HLA-DRB5 Chains / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D002352:Carrier Proteins; D059810:HLA-DR Serological Subtypes; D015798:HLA-DR1 Antigen; C421823:HLA-DR10 antigen; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; C487961:HLA-DRB1*01:01 antigen; C553505:HLA-DRB1*04:01 antigen; C489631:HLA-DRB1*15:01 antigen; D059847:HLA-DRB5 Chains; D018840:HSP70 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; C544374:LAMTOR1 protein, human; D051907:Lysosomal Membrane Proteins; D010455:Peptides; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; C085992:lipolysis-stimulated receptor