Analysis of physical interactions between peptides and HLA molecules and application to the detection of human immunodeficiency virus 1 antigenic peptides.
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.
Choppin
J
J
Institut National de la Santé et de la Recherche Médicale U152, Hôpital Cochin, Paris, France.
Martinon
F
F
Gomard
E
E
Bahraoui
E
E
Connan
F
F
Bouillot
M
M
Lévy
J P
JP
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*
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