Cutting Edge: Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B.
Although it is clear that KIR3DL1 recognizes Bw4(+) HLA-B, the role of Bw4(+) HLA-A allotypes as KIR3DL1 ligands is controversial. We therefore examined the binding of tetrameric HLA-A and -B complexes, including HLA*2402, a common Bw4(+) HLA-A allotype, to KIR3DL1*001, *005, *007, and *1502 allotypes. Only Bw4(+) tetramers bound KIR3DL1. Three of four HLA-A*2402 tetramers bound one or more KIR3DL1 allotypes and all four KIR3DL1 allotypes bound to one or more HLA-A*2402 tetramers, but with different binding specificities. Only KIR3DL1*005 bound both HLA-A*2402 and HLA-B*5703 tetramers. HLA-A*2402-expressing target cells were resistant to lysis by NK cells expressing KIR3DL1*001 or *005. This study shows that HLA-A*2402 is a ligand for KIR3DL1 and demonstrates how the binding of KIR3DL1 to Bw4(+) ligands depends upon the bound peptide as well as HLA and KIR3DL1 polymorphism.
Thananchai
Hathairat
H
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom.
Gillespie
Geraldine
G
Martin
Maureen P
MP
Bashirova
Arman
A
Yawata
Nobuyo
N
Yawata
Makoto
M
Easterbrook
Philippa
P
McVicar
Daniel W
DW
Maenaka
Katsumi
K
Parham
Peter
P
Carrington
Mary
M
Dong
Tao
T
Rowland-Jones
Sarah
S
D000483:Alleles; D000595:Amino Acid Sequence; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism*; D059871:HLA-A24 Antigen; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1
D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; C515083:KIR3DL1 protein, human; D008024:Ligands; D010455:Peptides; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1