title: Sampling of major histocompatibility complex class I-associated peptidome suggests relatively looser global association of HLA-B*5101 with peptides.
abstract: We have analyzed peptides associated with six human major histocompatibility complex (MHC) class I allomorphs expressed by the U937 cell line. Peptides were isolated by mild acid elution or by MHC class I immunoprecipitation by using W6/32 monoclonal antibody. Eighty-five peptides were sequenced by mass spectrometry, and their putative binding alleles were assigned using bioinformatic tools. Only three peptides isolated by the two approaches were identical, suggesting that the approaches may yield distinct partially overlapping peptide populations. Mild acid treatment-derived peptides manifested overall characteristics suggestive of relatively lower affinity of binding for MHC class I. Interestingly, a large proportion of putative HLA-B*5101-binding peptides was evident among the mild acid treatment-eluted peptides, and to a lesser degree in the affinity-purified peptide pool. These results suggest that HLA-B*5101 may bind a potentially large pool of peptides with relatively lower affinity. We suggest that lower affinity of peptide binding may be the basis for inefficient tolerance to HLA-B*5101-binding self-peptides, a predisposing factor for the development of Behçet disease.
authors.affiliation: Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010-2970, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gebreselassie
authors.forename: Hans
authors.initials: H
authors.lastname: Spiegel
authors.forename: Stanislav
authors.initials: S
authors.lastname: Vukmanovic
mesh_terms: D000595:Amino Acid Sequence; D001528:Behcet Syndrome / Q000276:immunology; D001665:Binding Sites / Q000235:genetics; D015235:HLA-B Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020298:U937 Cells
chemical_list: D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides