Peptide binding to HLA-DR1: a peptide with most residues substituted to alanine retains MHC binding.
Major histocompatibility complex (MHC) glycoproteins play an important role in the development of an effective immune response. An important MHC function is the ability to bind and present 'processed antigens' (peptides) to T cells. We show here that the purified human class II MHC molecule, HLA-DR1, binds peptides that have been shown to be immunogenic in vivo. Detergent-solubilized HLA-DR1 and a papain-cleaved form of the protein lacking the transmembrane and intracellular regions have similar peptide binding properties. A total of 39 single substitutions were made throughout an HLA-DR1 restricted hemagglutinin epitope and the results determine one amino acid in this peptide which is crucial to binding. Based on this analysis, a synthetic peptide was designed containing two residues from the original hemagglutinin epitope embedded in a chain of polyalanine. This peptide binds to HLA-DR1, indicating that the majority of peptide side chains are not required for high affinity peptide binding.
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
T S
TS
Jardetzky
J C
JC
Gorga
R
R
Busch
J
J
Rothbard
J L
JL
Strominger
D C
DC
Wiley
D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000378:metabolism*; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D010206:Papain; D051381:Rats; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology*
D015798:HLA-DR1 Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; C031540:M-protein, influenza virus; D014763:Viral Matrix Proteins; D010206:Papain; D000409:Alanine