Human B cells secrete migration inhibition factor (MIF) and present a naturally processed MIF peptide on HLA-DRB1*0405 by a FXXL motif.
A better knowledge of peptide structures interacting with major histocompatibility complex (MHC) molecules is of great interest for better understanding of the molecular basis of immune recognition. We have isolated naturally processed peptides from a continuously growing antigen-presenting Epstein-Barr virus-transformed human B-cell line. HLA-DR complexes were purified by specific affinity chromatography and complexed peptides were released by acid treatment. The isolated peptides were separated by reversed phase chromatography and fractions were analysed by Edman degradation at picomolar ranges. From 30 fractions that were examined seven peptides bound to the HLA-DRB1*0405 and two peptides from the human leucocyte antigen (HLA) class II associated invariant chain bound to HLA-DRB1*1302. In addition, a N-terminal beta-chain peptide of the 0405 allele was identified. Evaluation of amino acid sequences revealed a refined FXXL motif for the 0405 allele, in which F (phenylalanine) stands for any aromatic amino acid and L (leucine) can be exchanged by either I (isoleucine) or V (valine). In total, three fractions contained a peptide derived from the human migration inhibition factor (MIF), a pro-inflammatory cytokine that is normally produced by activated T lymphocytes and monocytes/macrophages. Indeed, cytokine analysis revealed high amounts of MIF secreted by the B-cell line, confirming that MHC class II expressing cells can present any intrinsic peptide that contains the distinct motif for HLA-binding. For MIF, the amino acid sequence Y36IAV39 represents the required binding motif for HLA-DRB1*0405. Nevertheless, it is the first time that cytokine fragments were found to bind to HLA molecules on human B cells.
Wymann
D
D
Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
Blüggel
M
M
Kalbacher
H
H
Blesken
T
T
Akdis
C A
CA
Meyer
H E
HE
Blaser
K
K
D000483:Alleles; D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics; D059811:HLA-DRB1 Chains; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007961:Leukocyte Migration-Inhibitory Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007961:Leukocyte Migration-Inhibitory Factors