Beta 2-microglobulin-free HLA class I heavy chain epitope mimicry by monoclonal antibody HC-10-specific peptide
Autor: | Soldano Ferrone, Elvira Favoino, Franco Dammacco, Federico Perosa, G Luccarelli, Marcella Prete |
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Rok vydání: | 2003 |
Předmět: |
Models
Molecular medicine.drug_class Immunology Amino Acid Motifs Peptide Monoclonal antibody Binding Competitive Epitope Cell Line Mice Antigen Antibody Specificity HLA Antigens medicine Tumor Cells Cultured Immunology and Allergy Animals Humans Computer Simulation Beta (finance) chemistry.chemical_classification Mice Inbred BALB C biology Beta-2 microglobulin Chemistry Histocompatibility Antigens Class I Molecular Mimicry Antibodies Monoclonal Molecular biology Peptide Fragments Amino acid Protein Subunits biology.protein Female Binding Sites Antibody Antibody beta 2-Microglobulin Epitope Mapping Injections Intraperitoneal Bacteriophage M13 Protein Binding |
Zdroj: | Scopus-Elsevier |
ISSN: | 0022-1767 |
Popis: | mAb HC-10 loses its reactivity with HLA class I (HLA-I) H chain (HC) following its association with β2-microglobulin (β2m). Furthermore, the HC-10 defined epitope appears to be involved in the pathogenesis of spondyloarthropathies, because HC-10 reduced their incidence in HLA-B27+β2m°/MHC class II knockout mice. This study has characterized the determinant recognized by HC-10. Panning of a phage display peptide library with HC-10 resulted in isolation of the motif PxxWDR, which could be aligned with P57, W60, D61, and R62 of the first domain of the HLA-I HC allospecificities reactive with HC-10. The 55EGPEYWDR(N/E)T64 (p-1) is the shortest motif-bearing peptide that reacts with HC-10 and inhibits its binding to soluble HLA-B7 HC, irrespective of whether N (p-1a) or E (p-1b) is present at position 63. By contrast, HC-10 did not react with six additional peptides, each bearing motif amino acid substitutions present in HC-10-not-reactive HLA-I allospecificities. The p-1-derived Qp-1, synthesized with the additional conserved Q54, which displays the highest in vitro reactivity with HC-10, was the only one to induce in mice IgG resembling HC-10 in their fine specificity. Mapping of the HC-10-defined determinant suggests that the lack of mAb reactivity with β2m-associated HLA-I HC is caused by blocking by the peptide in the groove of β2m-associated HLA-I HC, though a role of HC conformational changes following its association with β2m cannot be excluded. This information contributes to our understanding of the molecular basis of the antigenic profiles of β2m-free and β2m-associated HLA-I HC and may serve to develop active specific immunotherapy of spondyloarthropathies. |
Databáze: | OpenAIRE |
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