Matched Sizes of Activating and Inhibitory Receptor/Ligand Pairs Are Required for Optimal Signal Integration by Human Natural Killer Cells

PLoS One

Stephane Oddos¹  Karsten Köhler¹  Maryam Mehrabi¹  Daniel M. Davis¹  Philipp Eissmann¹  Shiqiu Xiong²  Philip Anton van der Merwe²  Shaun-Paul Cordoba²  Alice Harrison²  Nigel J. Burroughs³  Vladimir Miloserdov³  Joanna Brzostek⁴  Keith Gould⁴ 

[1] Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom;Sir William Dunn School of Pathology, Oxford University, Oxford, United Kingdom;Warwick Systems Biology Centre, University of Warwick, Coventry, United Kingdom;Wright-Fleming Institute, Imperial College London, London, United Kingdom

关键词: NK cells;    Immune receptor signaling;    Signal inhibition;    Synapses;    Flow cytometry;    Phosphorylation;    Cell binding;    Secretion;   

DOI  :  10.1371/journal.pone.0015374

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions.

【 授权许可】

CC BY