Diverse functionality among human NK cell receptors for the C1 epitope of HLA-C: KIR2DS2, KIR2DL2, and KIR2DL3
- 1Genome Analysis Unit, Discovery Research, Amgen Inc., South San Francisco, CA, USA
- 2Department of Structural Biology, Stanford University, Stanford, CA, USA
Interactions between killer immunoglobulin-like receptors (KIRs) and their HLA-A, -B, and -C ligands diversify the functions of human natural killer cells. Consequently, combinations of KIR and HLA genotypes affect resistance to infection and autoimmunity, success of reproduction and outcome of hematopoietic cell transplantation. HLA-C, with its C1 and C2 epitopes, evolved in hominids to be specialized KIR ligands. The system’s foundation was the C1 epitope, with C2 a later addition, by several million years. The human inhibitory receptor for C1 is encoded by KIR2DL2/3, a gene having two divergent allelic lineages: KIR2DL2 is a B KIR haplotype component and KIR2DL3 an A KIR haplotype component. Although KIR2DL2 and KIR2DL3 exhibit quantitative differences in specificity and avidity for HLA-C, they qualitatively differ in their genetics, functional effect, and clinical influence. This is due to linkage disequilibrium between KIR2DL2 and KIR2DS2, a closely related activating receptor that was selected for lost recognition of HLA-C.
Keywords: killer cells, natural, killer cell immunoglobulin-like receptor, receptor–ligand interaction, disease association, structure–function relationship
Citation: Moesta AK and Parham P (2012) Diverse functionality among human NK cell receptors for the C1 epitope of HLA-C: KIR2DS2, KIR2DL2, and KIR2DL3. Front. Immun. 3:336. doi:10.3389/fimmu.2012.00336
Received: 04 July 2012; Accepted: 22 October 2012;
Published online: 22 November 2012.
Copyright: © 2012 Moesta and Parham. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Achim K. Moesta, Genome Analysis Unit, Discovery Research, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. e-mail: email@example.com;Peter Parham, Department of Structural Biology, Stanford University, 299 Campus Drive West, Fairchild D-157, Stanford, CA 94305, USA. e-mail: firstname.lastname@example.org