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Epstein-Barr Virus Peptides Derived from Latent Cycle Proteins Prevent the Inhibition of NKG2A Expressing NK Cells

45 Pages Posted: 20 Apr 2020 Sneak Peek Status: Under Review

See all articles by Berenice Mbiribindi

Berenice Mbiribindi

Stanford University - Division of Abdominal Transplantation

Josselyn K. Pena

Stanford University - Division of Abdominal Transplantation

Matthew P. Arvedson

Stanford University - Division of Abdominal Transplantation

Olivia L. Hatton

Colorado College

Carlos O. Esquivel

Stanford University - Division of Abdominal Transplantation

Olivia M. Martinez

Stanford University - Division of Abdominal Transplantation

Sheri M. Krams

Stanford University - Division of Abdominal Transplantation

More...

Abstract

Natural killer (NK) cells control viral infection through the interaction between inhibitory receptors and human leukocyte antigen (HLA) ligands and bound peptide. NK cells expressing the inhibitory receptor NKG2A/CD94 recognize and respond to autologous B cells latently infected with Epstein–Barr virus (EBV). The mechanism is not yet understood, thus we investigated peptides derived from the seven latent proteins of EBV in the interaction of NKG2A and its ligand HLA-E. Functional analysis demonstrated that EBV peptides can bind to HLA-E and block inhibition of NK cell effector function. Moreover, analysis of DNA from 79 subjects showed sequence variations in the latent protein, LMP1, which alters NK responses to EBV. We provide evidence that peptides derived from EBV latent cycle proteins can impair the recognition of NKG2A despite being presented by HLA-E, resulting in NK cell activation. Thus, blocking of the NKG2A-HLA-E axis with viral peptides may have therapeutic potential.

Keywords: NK cells, EBV, peptide presentation, HLA-E, NKG2A

Suggested Citation

Mbiribindi, Berenice and Pena, Josselyn K. and Arvedson, Matthew P. and Hatton, Olivia L. and Esquivel, Carlos O. and Martinez, Olivia M. and Krams, Sheri M., Epstein-Barr Virus Peptides Derived from Latent Cycle Proteins Prevent the Inhibition of NKG2A Expressing NK Cells. Available at SSRN: https://ssrn.com/abstract=3570561 or http://dx.doi.org/10.2139/ssrn.3570561
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Berenice Mbiribindi (Contact Author)

Stanford University - Division of Abdominal Transplantation ( email )

United States

Josselyn K. Pena

Stanford University - Division of Abdominal Transplantation ( email )

United States

Matthew P. Arvedson

Stanford University - Division of Abdominal Transplantation ( email )

United States

Olivia L. Hatton

Colorado College ( email )

14 East Cache La Poudre Street
Colorado Springs, CO 80903
United States

Carlos O. Esquivel

Stanford University - Division of Abdominal Transplantation

United States

Olivia M. Martinez

Stanford University - Division of Abdominal Transplantation ( email )

United States

Sheri M. Krams

Stanford University - Division of Abdominal Transplantation ( email )

United States

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