title: Analysis of physical interactions between peptides and HLA molecules and application to the detection of human immunodeficiency virus 1 antigenic peptides.
abstract: The physical association of 40 antigenic peptides and purified HLA class I and class II molecules was monitored using a direct peptide binding assay (PBA) in solid phase and an inhibition peptide binding assay (IPBA) in which the competing peptide was present in a soluble phase. We also examined the ability of different peptides to inhibit the lytic activity of human antiviral cytolytic T cells towards cells incubated with the corresponding target peptide. Our results showed that: (a) Binding of a given human T cell-recognized peptide to several HLA class I and class II molecules occurred frequently. Nevertheless, preferential binding of peptides to their respective restriction molecules was also observed. (b) Binding of HLA molecules to peptides recognized by murine T cells occurred less frequently. (c) 11 of 24 (46%) randomly selected HIV-1 peptides contained agretopic residues allowing their binding to HLA molecules. (d) The kinetics of HLA/peptide association depended on the peptide tested and were faster than or similar to those reported for Ia molecules. Dissociation of these complexes was very low. (e) Peptide/HLA molecule binding was dependent on length, number of positive charges, and presence of hydrophobic residue in the peptide. (f) A correlation was demonstrated between a peptide inhibitory effect in the IPBA and its blocking effect in the cytolytic test. Our data indicated that the restriction phenomenon observed in T cell responses was not strictly related to either an elective HLA/peptide association, or a high binding capacity of a peptide to HLA molecules. These data also showed that the PBA and IPBA are appropriate for the detection of agretopic residues within HIV-1 proteins.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U152, Hôpital Cochin, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Choppin
authors.forename: F
authors.initials: F
authors.lastname: Martinon
authors.forename: E
authors.initials: E
authors.lastname: Gomard
authors.forename: E
authors.initials: E
authors.lastname: Bahraoui
authors.forename: F
authors.initials: F
authors.lastname: Connan
authors.forename: M
authors.initials: M
authors.lastname: Bouillot
authors.forename: J P
authors.initials: JP
authors.lastname: Lévy
mesh_terms: D000595:Amino Acid Sequence; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D014764:Viral Proteins