Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Apr;156(4):319-328.
doi: 10.1111/imm.13039. Epub 2019 Jan 17.

Conserved and variable natural killer cell receptors: diverse approaches to viral infections

Leidy Y Bastidas-Legarda  1 , Salim I Khakoo  1
Affiliations
Review

Conserved and variable natural killer cell receptors: diverse approaches to viral infections

Leidy Y Bastidas-Legarda et al. Immunology. 2019 Apr.

Abstract

Natural killer (NK) cells are lymphocytes of the innate immune system with essential roles during viral infections. NK cell functions are mediated through a repertoire of non-rearranging inhibitory and activating receptors that interact with major histocompatibility complex (MHC)-peptide complexes on the surface of infected cells. Recent work studying the conserved CD94-NKG2A and variable killer cell immunoglobulin-like receptor-MHC systems suggest that these two receptor families may have subtly different properties in terms of interactions with MHC class I bound peptides, and in recognition of down-regulation of MHC class I. In this review, we discuss how these properties generate diversity in the NK cell response to viruses.

Keywords: conserved; natural killer cells; polymorphic; receptor-ligand; viral infection.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Activating and inhibitory natural killer (NK) cell receptors and their major histocompatibility complex (MHC) class I ligands. Shown are the different interactions between the killer cell immunoglobulin‐like receptors (KIR) and CD94:NKG2 family of receptors and their MHC class I ligands. LILRB1 interacts with folded HLA class I molecules, HLA‐F and HLA‐G. KIR2DL4 is thought to interact with HLA‐G through an endosomal compartment. HLA‐F binds as an open conformer to KIR3DS1, KIR2DS4 and KIR3DL2.
Figure 2
Figure 2
Comparison of how changes in major histocompatibility complex (MHC) expression and presentation of peptides differentially affect CD94:NKG2 and killer cell immunoglobulin‐like receptor (KIR) interactions with MHC class I. Variations in MHC class I levels have more profound effects on inhibition through CD94:NKG2A than through inhibitory KIR whereas changes in the peptide content of MHC class I are more likely to lead through activation of natural killer (NK) cells expressing KIR.
Figure 3
Figure 3
Effects of DNA and RNA viruses on polymorphic and non‐polymorphic MHC class I molecules, demonstrating their potential for engagement of activating or inhibitory natural killer (NK) cell receptors. KIR3DS1 and KIR3DL2 are polymorphic, but bind the open conformer of HLA‐F, which is up‐regulated by both human immunodeficiency virus type 1 (HIV‐1) and hepatitis C virus (HCV). KIR2DS2 interacts with complexes formed by HLA‐C and flaviviruses or HCV‐derived peptides.
See this image and copyright information in PMC

References

    1. Gasteiger G, D'Osualdo A, Schubert DA, Weber A, Bruscia EM, Hartl D. Cellular innate immunity: an old game with new players. J Innate Immun 2017; 9:111–25. - PMC - PubMed
    1. Woolhouse ME, Webster JP, Domingo E, Charlesworth B, Levin BR. Biological and biomedical implications of the co‐evolution of pathogens and their hosts. Nat Genet 2002; 32:569–77. - PubMed
    1. Beltrame LM, Sell AM, Moliterno RA, Clementino SL, Cardozo DM, Dalalio MM et al Influence of KIR genes and their HLA ligands in susceptibility to dengue in a population from southern Brazil. Tissue Antigens 2013; 82:397–404. - PubMed
    1. Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J et al HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 2004; 305:872–4. - PubMed
    1. Hernandez‐Ramirez D, Esparza‐Perez MA, Ramirez‐Garcialuna JL, Arguello JR, Mandeville PB, Noyola DE et al Association of KIR3DL1/S1 and HLA‐Bw4 with CD4 T cell counts in HIV‐infected Mexican mestizos. Immunogenetics 2015; 67:413–24. - PubMed

Publication types

MeSH terms

Substances