Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene.
Human natural killer (NK) cells with the CD3- CD16+ phenotype recognize allospecificities on normal T-cell blasts. The NK-defined specificity 1 (NK-1) is recessively inherited and has been mapped to the major histocompatibility complex between the complement gene cluster and HLA-A. A gene for NK-1, however, has not been identified. Here we demonstrate that NK-1 and the recently defined NK specificity 2 (NK-2) are reciprocally associated with homozygosity for a diallelic polymorphism at amino acid positions 77 and 80 in the putative peptide-binding site of HLA-C (P less than 10(-5)). NK-cell recognition of allogeneic cells may, therefore, be controlled by HLA-C itself or by a closely linked gene(s), which dominantly prevents (resistance alleles) or recessively permits (susceptibility alleles) recognition of still-unknown target determinants.
Colonna
M
M
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Spies
T
T
Strominger
J L
JL
Ciccone
E
E
Moretta
A
A
Moretta
L
L
Pende
D
D
Viale
O
O
D001483:Base Sequence; D002874:Chromosome Mapping; D005805:Genes, MHC Class I; D008040:Genetic Linkage; D015236:HLA-C Antigens / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction
D015236:HLA-C Antigens; D009838:Oligodeoxyribonucleotides