HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells.
Natural killer (NK) cells recognize alloantigens on normal cells. One of these alloantigens correlates with homozygosity for a dimorphism of HLA-C at positions 77-80, which is shared by a number of HLA-C alleles. A second allelic alloantigen correlates with homozygosity for the alternative HLA-C dimorphism, which is shared by the remaining HLA-C alleles. Moreover, NK1- and NK2-specific NK cell lines can be generated by mixed leukocyte cultures in which donor and stimulator are homozygous for the alternative dimorphisms at positions 77-80 of HLA-C. In the present work, the role of HLA-C in NK cell-mediated allorecognition was directly investigated by analyzing the effects produced by transfection of several HLA-C alleles on NK sensitivity of class I-deleted mutant cell lines. Transfection of cells with HLA-C alleles encoding Asn-77-Lys-80 (including HLA-Cw4, -Cw5, and -Cw6) inhibited the lysis of the targets by NK1-specific NK cells, whereas HLA-C alleles encoding Ser-77-Asn-80 (including HLA-Cw1, -Cw7, and -Cw13) protected the targets from NK2-specific NK cells. Thus, HLA-C alleles are the dominant inhibitory ligands that protect targets from lysis by these allospecific NK cells.
Colonna
M
M
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Borsellino
G
G
Falco
M
M
Ferrara
G B
GB
Strominger
J L
JL
D000483:Alleles; D000595:Amino Acid Sequence; D001216:Asparagine; D001402:B-Lymphocytes; D002460:Cell Line; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic; D017353:Gene Deletion; D005805:Genes, MHC Class I; D015236:HLA-C Antigens / Q000235:genetics* / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007519:Isoantigens / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex; D017354:Point Mutation; D012694:Serine; D014162:Transfection
D015236:HLA-C Antigens; D007519:Isoantigens; D012694:Serine; D001216:Asparagine