Publication

Title: Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1
Authors: Martin MP, Naranbhai V, Shea PR, Qi Y, Ramsuran V, Vince N, Gao X, Thomas R, Brumme ZL, Carlson JM, Wolinsky SM, Goedert JJ, Walker BD, Segal FP, Deeks SG, Haas DW, Migueles SA, Connors M, Michael N, Fellay J, Gostick E, Llewellyn-Lacey S, Price DA, Lafont BA, Pymm P, Saunders PM, Widjaja J, Wong SC, Vivian JP, Rossjohn J, Brooks AG, Carrington M.
Journal: J Clin Invest.,pii: 98463. doi: 10.1172/JCI98463: (2018)

Journal Impact Factor (I.F.): 12.784
Number of citations (Google Scholar): 1

Abstract

HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in level of HIV control among B*57+ individuals.

Using whole genome sequencing of untreated B*57+ HIV-1 infected controllers and non-controllers, 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 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 track one another nearly perfectly, and two KIR3DL1 allotypes differing only at these three positions showed significant differences in binding B*57:01 tetramers, where the protective allotype showed lower binding.

Thus, variation in an immune natural killer cell receptor that binds B*57:01 modifies its protection. These data speak to exquisite specificity of KIR-HLA interactions in human health and disease

Download: Full text paper

Citation: Martin MP, Naranbhai V, Shea PR, Qi Y, Ramsuran V, Vince N, Gao X, Thomas R, Brumme ZL, Carlson JM, Wolinsky SM, Goedert JJ, Walker BD, Segal FP, Deeks SG, Haas DW, Migueles SA, Connors M, Michael N, Fellay J, Gostick E, Llewellyn-Lacey S, Price DA, Lafont BA, Pymm P, Saunders PM, Widjaja J, Wong SC, Vivian JP, Rossjohn J, Brooks AG, Carrington M. Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1 J Clin Invest.,pii: 98463. doi: 10.1172/JCI98463: (2018).

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