Epstein-Barr Virus (EBV)-lytic Cross-reactive Influenza-A (IAV) Memory CD8 T-cells in EBV Sero-negative Middle-aged Adults
Watkin, Levi B.
Ruiz De Luzuriaga, Katherine
Selin, Liisa K.
Document TypePoster Abstract
KeywordsImmunology of Infectious Disease
Translational Medical Research
MetadataShow full item record
AbstractEBV is a common human pathogen, which infects ~90% of people and establishes a life-long chronic infection. The clinical outcomes of acute infection can range from asymptomatic to severe immunopathology such as infectious mononucleosis (IM). However, for unknown reasons 5-10% of middle-aged adults (>35 years) remain EBV-seronegative (EBV-SN) when the virus infects the vast majority of people, and is actively shed at high titers during chronic infection. Here we show that EBV-SN (ASN) HLA-A2+ middle-aged adults possess a unique IAV-M1-GIL58-66 memory CD8 T-cell response that cross-reacts with EBV lytic epitopes that differs from teenage EBV-SN (TSN) (18-19 years) and EBV-seropositive (EBV-SP) adult donors. The five tested HLA-A2+ EBV-SN middle-aged adults had a significantly increased IAV-M158-66-GIL tetramer+ CD8 frequency compared to EBV-SP donors. Upon exposure to EBV antigens in vitro both IAV-M158-66GIL/EBV-BMLF1280-288-GLC and IAV-M158-66-GIL/EBV-BRLF1109-117-YVL, functionally cross-reactive CD8+ responses could be detected in the peripheral blood of middle-aged EBV-SN donors, while only IAV-M1/EBV-YVL cross-reactive responses were detected in some teenage EBV-SN or EBV-seropositive people . Surprisingly, these IAV-M1-GIL-specific CD8 T-cells in middle-aged EBV-SN adults expanded dramatically to EBV lytic antigens and produced cytokines at high functional avidity. They lysed EBV-infected targets and showed potential (by CD103 expression) to enter mucosal epithelial tissue where infection initiates. Additionally, these cross-reactive cells had an oligo-clonal T-cell receptor repertoire different than EBV-SP donors. Taken together these data suggest that an altered cross-reactive T cell repertoire could mediate protective immunity against viral infection. Our results imply that sero-negative adults might have the ability to resist viral infection via heterologous immunity. (NIH-AI49320).
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/27980
Abstract of poster presented at the 2014 UMass Center for Clinical and Translational Science Research Retreat, held on May 20, 2014 at the University of Massachusetts Medical School, Worcester, Mass.
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