Journal article

Polymorphism in human cytomegalovirus UL40 impacts on recognition of human leukocyte antigen-E (HLA-E) by natural killer cells

SL Heatley, G Pietra, J Lin, JML Widjaja, CM Harpur, S Lester, J Rossjohn, J Szer, A Schwarer, K Bradstock, PG Bardy, MC Mingari, L Moretta, LC Sullivan, AG Brooks

Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2013

Abstract

Natural killer (NK) cell recognition of the nonclassical human leukocyte antigen (HLA) molecule HLA-E is dependent on the presentation of a nonamer peptide derived from the leader sequence of other HLA molecules to CD94-NKG2 receptors. However, human cytomegalovirus can manipulate this central innate interaction through the provision of a "mimic" of the HLA-encoded peptide derived from the immunomodulatory glycoprotein UL40. Here, we analyzed UL40 sequences isolated from 32 hematopoietic stem cell transplantation recipients experiencing cytomegalovirus reactivation. The UL40 protein showed a "polymorphic hot spot" within the region that encodes the HLA leader sequence mimic. Although all seq..

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Grants

Funding Acknowledgements

This work was supported by grants from the National Health and Medical Research Council, a career development award from the National Health and Medical Research Council (to L. C. S.), and an Australia fellowship from the National Health and Medical Research Council (to J. R.).