The structure and expression of genes encoding serologically undetected HLA-C locus antigens.
Approximately 20 to 50% individuals in every race are untypable by human alloantisera for at least one allele of HLA-C locus and the surface expression of HLA-C locus Ag in such an individual (HLA-C blank Ag) remains unknown. To investigate the structure and the surface expression of HLA-C blank Ag, two genes (Cb-1 and Cb-2) encoding HLA-C blank Ag were cloned and their primary structures were determined and compared with other HLA-C locus genes. The similarity of amino acids between Cb-1 and Cw1 was the highest among HLA-C locus genes previously published. Five amino acid substitutions between these molecules were shown to be located on the beta-strand of alpha 1 and alpha 2 domains, suggesting that they might change the conformational allodeterminants on the alpha-helical region of Cw1 which were recognized by antibodies. On the other hand, Cb-2 was the closest to Cw2.2. Six of nine amino acid substitutions between these molecules were observed on alpha 1 and alpha 2 domains, whereas three other substitutions were located on the leader peptide, the alpha 3 domain and the transmembrane. Two substitutions (residues 73 and 163) of the alpha-helical region of the alpha 1 and alpha 2 domains and one (residue 16) of exposed loop may make new allodeterminants which are not recognized by anti-Cw2 sera as well as other alloantisera. The surface expression of these genes was examined on transfected mouse L cells and human B cell line. Both gene products were expressed stably on the surface of these cells. These results suggest that HLA-C blank Ag are most probably expressed on cells in HLA-C blank individuals and that the primary structures of these Ag, which were not detectable by the available alloantisera, may be incapable of generating corresponding alloantibodies.
Takiguchi
M
M
Department of Immunology, University of Tokyo, Japan.
Nishimura
I
I
Hayashi
H
H
Karakl
S
S
Kariyone
A
A
Kano
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000302:isolation & purification; D001402:B-Lymphocytes / Q000032:analysis; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D005796:Genes; D005805:Genes, MHC Class I; D015236:HLA-C Antigens / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D000954:Antigens, Surface; D015236:HLA-C Antigens