Humans differ from other hominids in lacking an activating NK cell receptor that recognizes the C1 epitope of MHC class I.
Modulation of human NK cell function by killer cell Ig-like receptors (KIR) and MHC class I is dominated by the bipartite interactions of inhibitory lineage III KIR with the C1 and C2 epitopes of HLA-C. In comparison, the ligand specificities and functional contributions of the activating lineage III KIR remain poorly understood. Using a robust, sensitive assay of KIR binding and a representative panel of 95 HLA class I targets, we show that KIR2DS1 binds C2 with ~50% the avidity of KIR2DL1, whereas KIR2DS2, KIR2DS3, and KIR2DS5 have no detectable avidity for C1, C2, or any other HLA class I epitope. In contrast, the chimpanzee has activating C1- and C2-specific lineage III KIR with strong avidity, comparable to those of their paired inhibitory receptors. One variant of chimpanzee Pt-KIR3DS2, the activating C2-specific receptor, has the same avidity for C2 as does inhibitory Pt-KIR3DL4, and a second variant has ~73% the avidity. Chimpanzee Pt-KIR3DS6, the activating C1-specific receptor, has avidity for C1 that is ~70% that of inhibitory Pt-KIR2DL6. In both humans and chimpanzees we observe an evolutionary trend toward reducing the avidity of the activating C1- and C2-specific receptors through selective acquisition of attenuating substitutions. However, the extent of attenuation has been extreme in humans, as exemplified by KIR2DS2, an activating C1-specific receptor that has lost all detectable avidity for HLA class I. Supporting such elimination of activating C1-specific receptors as a uniquely human phenomenon is the presence of a high-avidity activating C1-specific receptor (Gg-KIR2DSa) in gorilla.
Moesta
Achim K
AK
Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Graef
Thorsten
T
Abi-Rached
Laurent
L
Older Aguilar
Anastazia M
AM
Guethlein
Lisbeth A
LA
Parham
Peter
P
D000818:Animals; D005075:Biological Evolution; D000939:Epitopes / Q000276:immunology; D006071:Gorilla gorilla; D015236:HLA-C Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D002679:Pan troglodytes; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D015236:HLA-C Antigens; C433932:KIR2DS2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054340:Receptors, KIR
J Immunol. 1998 Jul 15;161(2):571-7
9670929
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14326-31
9826699
J Exp Med. 2003 Apr 7;197(7):933-8
12668644
Immunity. 2000 Jun;12(6):687-98
10894168
Blood. 2008 Sep 15;112(6):2369-80
18583565
Blood. 2010 Oct 7;116(14):2411-9
20581313
Annu Rev Immunol. 1996;14:619-48
8717527
J Exp Med. 2009 Oct 26;206(11):2557-72
19858347
Semin Immunol. 2008 Dec;20(6):321-30
18595730
Eur J Immunol. 1997 Dec;27(12):3095-9
9464792
Transplantation. 2003 Jan 15;75(1):43-9
12544869
Annu Rev Immunol. 2002;20:853-85
11861620
Eur J Immunol. 2008 Aug;38(8):2284-9
18624290
Eur J Immunol. 2008 Dec;38(12):3474-86
19016529
Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13224-9
16141329
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
J Exp Med. 2005 Apr 18;201(8):1319-32
15837816
Immunity. 2008 Nov 14;29(5):675-8
19006692
Genes Immun. 2009 Mar;10(2):162-73
19005473
J Immunol. 2002 Jul 1;169(1):220-9
12077248
Blood. 2009 Jan 15;113(3):726-32
18945962
J Immunol. 2008 Mar 15;180(6):3969-79
18322206
J Immunol. 2004 Jan 1;172(1):356-69
14688344
Blood. 2010 Feb 11;115(6):1166-74
19903900
J Immunol. 2009 Mar 15;182(6):3628-37
19265141