Coevolution of killer cell Ig-like receptors with HLA-C to become the major variable regulators of human NK cells.
Interactions between HLA class I and killer cell Ig-like receptors (KIRs) diversify human NK cell responses. Dominant KIR ligands are the C1 and C2 epitopes of MHC-C, a young locus restricted to humans and great apes. C1- and C1-specific KIRs evolved first, being present in orangutan and functionally like their human counterparts. Orangutans lack C2 and C2-specific KIRs, but have a unique C1+C2-specific KIR that binds equally to C1 and C2. A receptor with this specificity likely provided the mechanism by which C2-KIR interaction evolved from C1-KIR while avoiding a nonfunctional intermediate, that is, either orphan receptor or ligand. Orangutan inhibitory MHC-C-reactive KIRs pair with activating receptors of identical avidity and specificity, contrasting with the selective attenuation of human activating KIRs. The orangutan C1-specific KIR reacts or cross-reacts with all four polymorphic epitopes (C1, C2, Bw4, and A3/11) recognized by human KIRs, revealing their structural commonality. Saturation mutagenesis at specificity-determining position 44 demonstrates that KIRs are inherently restricted to binding just these four epitopes, either individually or in combination. This restriction frees most HLA-A and HLA-B variants to be dedicated TCR ligands, not subject to conflicting pressures from the NK cell and T cell arms of the immune response.
Older Aguilar
Anastazia M
AM
Immunology Program, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Guethlein
Lisbeth A
LA
Adams
Erin J
EJ
Abi-Rached
Laurent
L
Moesta
Achim K
AK
Parham
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D057079:Pongo; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology*
D015236:HLA-C Antigens; D054340:Receptors, KIR
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14326-31
9826699
Cell. 1978 May;14(1):9-20
667938
J Immunol. 1982 Jan;128(1):129-35
6172474
Methods Mol Biol. 2000;121:239-50
10818730
J Exp Med. 1995 Aug 1;182(2):605-9
7629517
Nat Genet. 2007 Jun;39(6):733-40
17496894
Annu Rev Immunol. 2002;20:217-51
11861603
Semin Immunol. 2008 Dec;20(6):343-52
18635379
Hum Immunol. 2005 Sep;66(9):989-97
16360839
J Immunol. 1997 May 1;158(9):4026-8
9126959
Nat Genet. 2002 Aug;31(4):429-34
12134147
Immunogenetics. 1982;15(2):151-66
6174442
Nat Immunol. 2001 May;2(5):452-60
11323700
Nature. 2000 Jun 1;405(6786):537-43
10850706
Mol Immunol. 2002 May;38(14):1007-21
11955593
J Immunol. 1995 Sep 1;155(5):2306-10
7650366
Immunogenetics. 2006 Jan;57(12):904-16
16391939
J Immunol. 1998 Jul 15;161(2):571-7
9670929
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18692-7
19837691
Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4778-83
10781084
J Immunol. 2009 Mar 15;182(6):3618-27
19265140
PLoS Genet. 2009 Oct;5(10):e1000688
19834558
J Immunol. 2005 Oct 15;175(8):5222-9
16210627
Immunity. 2008 Nov 14;29(5):675-8
19006692
J Exp Med. 1996 Aug 1;184(2):735-40
8760827
Immunol Rev. 2006 Dec;214:56-72
17100876
J Exp Med. 2006 Mar 20;203(3):633-45
16533882
Mol Biol Evol. 2007 Jan;24(1):26-53
17047029
J Exp Med. 1995 Mar 1;181(3):1133-44
7532677
Immunity. 2000 Jun;12(6):687-98
10894168
Eur J Immunol. 2004 Jun;34(6):1673-9
15162437
Blood. 2008 Sep 15;112(6):2369-80
18583565
Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7983-5
1518825
J Immunol. 2007 Jan 15;178(2):647-51
17202323
Annu Rev Immunol. 1996;14:619-48
8717527
Nat Rev Immunol. 2006 Aug;6(8):584-94
16868549
Science. 1995 Apr 21;268(5209):405-8
7716543
Blood. 2007 Jul 15;110(2):578-86
17392508
J Immunol. 2002 Jul 1;169(1):220-9
12077248
Genome Res. 2005 Jan;15(1):25-35
15632087
Immunity. 1995 May;2(5):439-49
7749980
Nature. 2002 Apr 18;416(6882):726-9
11961552
Semin Immunol. 2008 Dec;20(6):311-6
19036608
J Immunol. 2002 Jan 1;168(1):240-52
11751968
Clin Exp Immunol. 2007 Jul;149(1):1-8
17521317
Immunol Res. 2008;41(3):267-94
18726714
J Exp Med. 2009 Oct 26;206(11):2557-72
19858347
Immunol Today. 2000 Dec;21(12):611-4
11114420
J Immunol. 1989 May 1;142(9):3320-8
2785140
Mol Immunol. 2005 Feb;42(4):471-5
15607801
Immunity. 1997 Dec;7(6):753-63
9430221
J Exp Med. 1994 Oct 1;180(4):1235-42
7931060
Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10160-5
20439706
Eur J Immunol. 1997 Dec;27(12):3095-9
9464792
Curr Biol. 1998 Jul 30-Aug 13;8(16):R582-8
9707399
J Immunol. 1986 Dec 1;137(11):3671-4
2431040
Exp Hematol. 1996 Feb;24(3):406-15
8599969
Blood. 2009 Jul 2;114(1):95-104
19304956
Blood. 2003 May 1;101(9):3730-40
12511415
Transplantation. 2003 Jan 15;75(1):43-9
12544869
Immunol Rev. 2008 Aug;224:98-123
18759923
J Med Primatol. 2010 Aug;39(4):194-212
20618586
Immunity. 2006 Aug;25(2):331-42
16901727
J Exp Med. 1992 Mar 1;175(3):709-18
1371301
Immunol Today. 1996 May;17(5):212-4
8991381
Immunity. 2005 Mar;22(3):295-304
15780987
J Exp Med. 1999 Apr 5;189(7):1093-100
10190900
Immunol Res. 2006;35(3):263-78
17172651
J Mol Biol. 1988 Jun 20;201(4):751-4
3172202
Immunogenetics. 2009 Jan;61(1):27-41
19009288
J Immunol. 2008 Mar 15;180(6):3969-79
18322206
J Immunol. 2004 Jan 1;172(1):356-69
14688344
J Immunol. 1996 May 1;156(9):3098-101
8617928
J Immunol. 2007 Jul 1;179(1):491-504
17579070
Immunol Rev. 2001 Oct;183:41-64
11782246
Blood. 2010 Feb 11;115(6):1166-74
19903900
Science. 2005 Oct 14;310(5746):300-4
16224019
J Exp Med. 1996 Aug 1;184(2):505-18
8760804
Blood. 2001 Aug 1;98(3):705-13
11468170
Immunogenetics. 2007 Jun;59(6):517-22
17450355
J Immunol. 2009 Mar 15;182(6):3628-37
19265141
Cancer Biol Ther. 2009 Dec;8(23):2211-20
19923897
Immunogenetics. 1999 Sep;49(10):865-71
10436180
Biochemistry (Mosc). 2006;71 Suppl 1:S60-4, 4-5
16487070
Annu Rev Immunol. 1998;16:359-93
9597134
Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13224-9
16141329
Semin Immunol. 2008 Dec;20(6):317-20
18656382