Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype.
Direct MHC binding assays with radiolabeled peptides and HLA class I-expressing mammalian cells such as EBV-transformed B cell lines and PHA-activated blasts have been developed. Significant binding of the radiolabeled probe could be obtained if the target cells were preincubated overnight at 26 degrees C in the presence of beta 2-microglobulin. Under these conditions, up to a few percent of the HLA molecules expressed by either cell type could be bound by the labeled peptides. With these assays, the degree of cross-reactivity of the A*0201-restricted hepatitis B virus core 18-27 peptide with other A2 subtypes was examined. It was determined that this peptide epitope also binds the A*0202, A*0205, and A*0206 but not A*0207 subtypes. Inhibition experiments with panels of synthetic peptide analogues underlined the similar ligand specificities of the HLA-A*0201, A*0202, and A*0205 alleles. Analysis of the polymorphic residues that help form the B and F pockets of various HLA alleles allowed prediction of binding of the hepatitis B virus core 18-27 epitope to two other HLA alleles (HLA-A*6802 and A*6901). Thus, it appears that a family of at least six different HLA-A molecules may share overlapping ligand specificities (aliphatic residues in position 2 and at the C termini). These results suggest that broadly cross-reactive peptide epitopes can be identified and greatly enhance the prospective feasibility of peptide-based vaccination approaches.
del Guercio
M F
MF
Cytel, San Diego, CA 92121.
Sidney
J
J
Hermanson
G
G
Perez
C
C
Grey
H M
HM
Kubo
R T
RT
Sette
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D004331:Drosophila melanogaster; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000145:classification / Q000378:metabolism*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011233:Precipitin Tests; D011485:Protein Binding / Q000276:immunology; D014162:Transfection
D000939:Epitopes; D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens; D010446:Peptide Fragments