Z Gastroenterol 2018; 56(01): E2-E89
DOI: 10.1055/s-0037-1612763
Lectures Session V Viral Hepatitis and Immunology – Saturday, January 27, 2018, 11:45am – 12:30pm, Lecture Hall A
Georg Thieme Verlag KG Stuttgart · New York

Characterization of the HEV-specific CD8 T-cell response in acute and chronic Hepatitis E virus infection

J Kemming
1   University Hospital Freiburg, Freiburg im Breisgau
2   Albert-Ludwigs University Freiburg, Faculty of Biology, Freiburg im Breisgau
,
M Panning
3   University Hospital Freiburg, Institute of Virology, Freiburg im Breisgau
,
S Pischke
4   UKE Hamburg, 1st Medical Clinic, Hamburg
,
J Schulze zur Wiesch
4   UKE Hamburg, 1st Medical Clinic, Hamburg
,
M Lütgehetmann
4   UKE Hamburg, 1st Medical Clinic, Hamburg
,
R Thimme
1   University Hospital Freiburg, Freiburg im Breisgau
,
C Neumann-Haefelin
1   University Hospital Freiburg, Freiburg im Breisgau
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2018 (online)

 

Introduction:

Hepatitis E Virus (HEV) infection is one of the leading causes of viral hepatitis worldwide. Immune competent individuals clear infection spontaneously, whereas in immune suppressed patients chronic infection can occur, ultimately leading to liver cirrhosis and Hepatocellular Carcinoma (HCC).

Aims:

In order to clear infection an effective virus-specific CD8 T-cell response is compulsory for other viral hepatitis viruses. For HEV infection this CD8 T-cell response to date has not been studied in detail. In this study we focused on the HEV-specific CD8 T cell response in acute and chronically HEV infected patients.

Methods:

We comprehensively studied the HEV-specific CD8 T-cell responses of 22 HEV-infected patients with antigen-specific expansion, functional testing and pMHCI-tetramer stainings. Of the 22 patients, 13 patients were acutely infected, 4 had a chronic HEV infection and 5 patients resolved HEV infection.

Results:

We identified the first 13 HEV-specific CD8 T-cell epitopes to date which are restricted by the HLA alleles A*01:01, A*02:01, A*03:01, B*27:05 and B*3501. We were able to detect HEV-specific CD8 T-cell responses in all resolvers and in the acutely infected patients, that contracted with time. The magnitude of the CD8 T-cell response varied according to the HLA allele by which it was restricted. The 4 HLA-B27 restricted epitopes mounted the highest CD8 T-cell responses. In HLA*B27 patients up to 40% of bulk CD8 T-cells stained ex vivo were specific for single HEV-specific epitopes. None of the chronic HEV Patients was HLA-B*27:05 positive. The HEV-specific CD8 T-cell response in the chronic patients was diminished in comparison to the acute disease course.

Conclusion:

Here we show a putative role for host factors like HLA alleles in HEV infection and that a strong and specific CD8 T-cell response is associated with viral clearance whereas a weak CD8 T-cell response is associated with viral persistence.