Molecular mapping of a new public HLA class I epitope shared by all HLA-B and HLA-C antigens and defined by a monoclonal antibody.
It has previously been shown that a mouse monoclonal antibody, designated 4E, reacts with an epitope common to all HLA-B and -C antigens and those of the HLA-Aw19 cross-reactive group, namely, HLA-A29, -A30, -A31, -A32, -Aw33, and -Aw74. In order to pinpoint the amino acid residues which comprise the public specificity recognized by 4E, and HLA-A29 cDNA clone was isolated and its predicted amino acid sequence compared with those of other cloned HLA class I genes. The isolated HLA-A29 cDNA corresponded to the rarer of the two A29 variant alleles, A29.1. Two amino acid residues of HLA-A29.1, gln-144 and arg-151, were found in all 24 HLA-B and HLA-C alleles examined but were present in only one of 15 HLA-A alleles for which sequence data are available. Importantly, this exceptional allele was HLA-A32, another member of the HLA-Aw19 cross-reactive group. Gln-144 and arg-151 should be capable of jointly contributing to the binding site for 4E, as they are situated in successive alpha-helical subregions and are predicted to be juxtaposed in the three-dimensional HLA molecule. Four other residues in the first or second external domains of HLA-A29.1 (thr-9, leu-62, gln-63, and his-102) were unique among the HLA-A alleles, but none of these was found in corresponding positions of HLA-B of -C alleles and thus failed to correlate with presence or absence of the 4E determinant. These observations are consistent with the notion that gln-144 and arg-151 define a determinant common to HLA-B, HLA-C, and the HLA-Aw19 cross-reactive group and the binding site of the monoclonal antibody 4E.
Trapani
J A
JA
Laboratory of Human Immunogenetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Mizuno
S
S
Kang
S H
SH
Yang
S Y
SY
Dupont
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D003001:Cloning, Molecular; D015342:DNA Probes; D000939:Epitopes / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D007525:Isoelectric Focusing; D051379:Mice; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D011233:Precipitin Tests; D014162:Transfection
D000911:Antibodies, Monoclonal; D015342:DNA Probes; D000939:Epitopes; D006680:HLA Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens