Identification of Immunogenic Epitopes That Permit the Detection of Antigen-Specific T Cell Responses in Multiple Serotypes of Group B Coxsackievirus Infections

Authors

Ninaad Lasrado, University of Nebraska - LincolnFollow
Arunakumar Gangaplara, University of Nebraska-LincolnFollow
Rajkumar Arumugam, University of Nebraska - LincolnFollow
Chandirasegara Massilamany, University of Nebraska-LincolnFollow
Sayli Pokal, University of Nebraska-LincolnFollow
Yuzhen Zhou, University of Nebraska - LincolnFollow
Shi-Hua Xiang, University of Nebraska - LincolnFollow
David Steffen, University of Nebraska-LincolnFollow
Jay Reddy, University of Nebraska - LincolnFollow

ORCID IDs

https://orcid.org/0000-0001-6762-2654 N. Lasrado

https://orcid.org/0000-0001-6307-9391 A. Gangaplara

https://orcid.org/0000-0002-5166-2296 D. Steffen

https://orcid.org/0000-0003-4082-9254 J. Reddy

Document Type

Article

Date of this Version

2020

Citation

Viruses 2020, 12, 347; www.mdpi.com/journal/viruses

doi:10.3390/v12030347

Comments

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license

Abstract

Coxsackievirus group B (CVB) contains six serotypes that can affect various organs. Some of these organ-specific diseases such as myocarditis and pancreatitis can be caused by more than one serotype. Thus, development of immunological tools common to multiple serotypes is desired. This is especially critical for analyzing antigen-specific T cell responses at a single cell level. To this end, we made efforts to identify the immunogenic epitopes of CVB3 leading us to localize three T cell epitopes within the viral protein 1 (VP1) namely, VP1 681–700, VP1 721–740 and VP1 771–790. First, we confirmed their immunogenicity in the immunization settings. Second, we sought to verify the ability of VP1 epitopes to bind major histocompatibility complex (MHC) class II (IAk) molecules. Third, we created MHC class II (IAk) dextramers and tetramers and ascertained the T cell responses to be antigen-specific. Fourth, we analyzed the T cell responses in animals infected with CVB3 and noted the magnitude of antigen-specific T cell responses occurring in the order of VP1 721–740 and VP1 681–700 followed by VP1 771–790 as verified by proliferation assay and IAk tetramer staining. All epitopes induced interferon (IFN)- as a major cytokine. Finally, we investigated whether the VP1 tools generated for CVB3 can also be used to verify T cell responses in infections caused by other serotypes. To this end, we established the CVB4 infection model in A/J mice and found that the CVB4 infection led to the induction of IFN- -producing T cell responses primarily for VP1 721–740 and VP1 681–700. Thus, the VP1-specific tools, particularly IAk tetramers can be used to monitor anti-viral T cell responses in multiple CVB serotypes.