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Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1

  1. Author:
    Martin, Pat
    Naranbhai, Vivek
    Shea, Patrick R.
    Qi, Ying
    Ramsuran, Veron
    Vince, Nicolas
    Gao, Xiaojiang
    Thomas, Rasmi
    Brumme, Zabrina L.
    Carlson, Jonathan M.
    Wolinsky, Steven M.
    Goedert, James J.
    Walker, Bruce D.
    Segal, Florencia P.
    Deeks, Steven G.
    Haas, David W.
    Migueles, Stephen A.
    Connors, Mark
    Michael, Nelson
    Fellay, Jacques
    Gostick, Emma
    Llewellyn-Lacey, Sian
    Price, David A.
    Lafont, Bernard A.
    Pymm, Phillip
    Saunders, Philippa M.
    Widjaja, Jacqueline
    Wong, Shu Cheng
    Vivian, Julian P.
    Rossjohn, Jamie
    Brooks, Andrew G.
    Carrington, Mary

  2. Author Address

    Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD 21704 USA.MIT & Harvard, Ragon Inst MGH, Boston, MA 02139 USA.Univ KwaZulu Natal, CAPRISA, Durban, South Africa.Columbia Univ, Inst Genom Med, New York, NY USA.Univ KwaZulu Natal, Sch Lab Med & Med Sci, KwaZulu Natal Res Innovat & Sequencing Platform K, Durban, South Africa.Univ Nantes, INSERM, UMR 1064, Ctr Rech Transplantat & Immunol,ATIP Avenir, Nantes, France.CHU Nantes, ITUN, Nantes, France.Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.Microsoft Res, Redmond, WA USA.Northwestern Univ, Div Infect Dis, Feinberg Sch Med, Chicago, IL 60611 USA.NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, NIH, Bethesda, MD 20892 USA.Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.San Francisco Gen Hosp, Med Ctr, San Francisco, CA 94110 USA.Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.Swiss Fed Inst Technol, Sch Life Sci, Lausanne, Switzerland.Cardiff Univ, Univ Hosp Wales, Sch Med, Heath Pk, Cardiff, S Glam, Wales.NIAID, Nonhuman Primate Immunogenet & Cellular Immunol U, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.NIAID, Viral Immunol Sect, Off Sci Director, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.Monash Univ, Infect & Immun Program, Clayton, Vic, Australia.Monash Univ, Dept Biochem & Mol Biol, Biomed Discovery Inst, Clayton, Vic, Australia.Monash Univ, Australian Res Council Ctr Excellence Adv Mol Ima, Clayton, Vic, Australia.Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Parkville, Vic, Australia.
    1. Year: 2018
    2. Date: May 01
  2. Journal: Journal of Clinical Investigation
  3. AMER SOC CLINICAL INVESTIGATION INC,
    1. 128
    2. 5
    3. Pages: 1903-1912
  5. Type of Article: Article
  6. ISSN: 0021-9738
  1. Abstract:

    HLA-B*57 control of HIV involves enhanced CD8(+) T cell responses against infected cells, but extensive heterogeneity exists in the level of HIV control among B*57(+) individuals. Using whole-genome sequencing of untreated B*57(+) HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection. The association was replicated in an independent cohort and across multiple outcomes. The modifying effect of I47V was confined to B*57:01 and was not observed for the closely related B*57:03. Positions 2, 47, and 54 tracked one another nearly perfectly, and 2 KIR3DL1 allotypes differing only at these 3 positions showed significant differences in binding B*57:01 tetramers, whereas the protective allotype showed lower binding. Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its protection. These data highlight the exquisite specificity of KIR-HLA interactions in human health and disease.

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  2. DOI: 10.1172/JCI98463
  3. PMID: 29461980
  4. PMCID: PMC5919796
  5. View record in Web of Science®
  6. WOS: 000431959100020

Library Notes

  1. Fiscal Year: FY2017-2018
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