KIR2DL2 Enhances Protective and Detrimental HLA Class I-Mediated Immunity in Chronic Viral Infection

PLoS Pathogens

Mary Carrington¹  Alison M. Vine²  Nafisa-Katrin Seich al Basatena²  Becca Asquith²  Charles R.M. Bangham²  Aidan MacNamara²  Chloe L. Thio³  Gregory D. Kirk³  Jacquie Astemborski³  Mitsuhiro Osame⁴  Koichiro Usuku⁵  James J. Goedert⁶  Salim I. Khakoo⁷  Sharyne M. Donfield⁸ 

[1] Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, United States of America;Imperial College, London, United Kingdom;Johns Hopkins University, Baltimore, Maryland, United States of America;Kagoshima University, Kagoshima, Japan;Kumamoto University, Kumamoto, Japan;National Cancer Institute, Rockville, Maryland, United States of America;Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America;Rho, Chapel Hill, North Carolina, United States of America

关键词: HTLV-1;    Viral load;    T cells;    Major histocompatibility complex;    Cytotoxic T cells;    Hepatitis C virus;    NK cells;    Viral transmission;    infection;   

DOI  :  10.1371/journal.ppat.1002270

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Killer cell immunoglobulin-like receptors (KIRs) influence both innate and adaptive immunity. But while the role of KIRs in NK-mediated innate immunity is well-documented, the impact of KIRs on theT cell responsein human disease is not known. Here we test the hypothesis that an individual's KIR genotype affects the efficiency of their HLA class I-mediated antiviral immune response and the outcome of viral infection. We show that, in two unrelated viral infections, hepatitis C virus and human T lymphotropic virus type 1, possession of the KIR2DL2 gene enhanced both protective and detrimental HLA class I-restricted anti-viral immunity. These results reveal a novel role for inhibitory KIRs. We conclude that inhibitory KIRs, in synergy with T cells, are a major determinant of the outcome of persistent viral infection.

【 授权许可】

CC BY