Peptide binding to empty HLA-B27 molecules of viable human cells.
Intracellular binding of antigenic peptides by polymorphic class I major histocompatibility complex molecules creates the ligands recognized by receptors of CD8+ T cells. Previously described in vitro assays of peptide binding to class I molecules have been limited by either the low proportion of accessible binding sites or the lack of allelic specificity. Here we describe a system in which the human class I molecule HLA-B27 binds considerable amounts of an influenza peptide with precise allelic discrimination. Binding requires viable cells, is stimulated by gamma-interferon and is inhibited by brefeldin A. Our results are consistent with the presence of fairly stable 'empty' HLA-B27 molecules at the cell surface. By contrast, analysis of the binding of a second influenza peptide indicates that empty HLA-Aw68 molecules are relatively short-lived. We speculate that HLA-B27 might bind extracellular peptides in vivo and that this property could underlie its association with autoimmune disease.
Benjamin
R J
RJ
Department of Cell Biology, Stanford University, California 94305-5400.
Madrigal
J A
JA
Parham
P
P
D000483:Alleles; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes; D001667:Binding, Competitive; D002460:Cell Line; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D015796:HLA-B27 Antigen; D010455:Peptides