Broad-Based CD4+ T Cell Responses to Influenza A Virus in a Healthy Individual Who Lacks Typical Immunodominance Hierarchy.

Li Chen,Damien Zanker,Kun Xiao,Sara Oveissi,Miaojuan Huang,Quanming Zou,Weisan Chen,Anjaleena Anthony,Chao Wu

doi:10.3389/fimmu.2017.00375

Abstract

Influenza A virus (IAV) infection is a significant cause of morbidity and mortality worldwide. CD4+ T cell responses have been shown to be important for influenza protection in mouse models and in human volunteers. IAV antigen-specific CD4+ T cell responses were found to focus on matrix 1 (M1) and nucleoprotein (NP) at the protein antigen level. At the epitope level, only several epitopes within M1 and NP were recognized by CD4+ T cells. And the epitope-specific CD4+ T cell responses showed a typical immunodominance hierarchy in most of the healthy individuals studied. In this study, we reported one case of atypical immunodominance hierarchy of CD4+ T cell responses to IAV. M1 and NP were still the immunodominant targets of CD4+ T cell responses. However, CD4+ T cell responses specific to 11 epitopes derived from M1 and NP were detected and showed no significant immunodominance hierarchy. Such an atypical pattern is likely determined by the individual’s HLA alleles. These findings will help us better understand the anti-IAV immunity as a whole and improve future vaccines against IAV.

Highlights

Influenza virus [influenza A virus (IAV)] infection is a global threat to human health
Using in vitro expanded multi-specificity Influenza A virus (IAV)-specific T cell lines and individual IAV protein antigens produced by recombinant vaccinia viruses, we have demonstrated that matrix 1 (M1) and nucleoprotein (NP) are the immunodominant antigens targeted by IAV-specific CD4+ T cells in healthy individuals (21)
To identify the dominant virus protein, multi-specificity, IAV-specific CD4+ T cell lines were generated by stimulating PBMCs in the presence of IL-2 with a soluble IAV antigen source generated by lysing IAV-infected P815 cells in 8 M urea

Summary

Introduction

Influenza virus [influenza A virus (IAV)] infection is a global threat to human health. About half a billion human beings have symptomatic influenza illness (1), and three to five million subjects suffer from severe influenza, causing approximately half a million deaths annually worldwide (2). Novel vaccines that are more effective and covering a broader spectrum of influenza viruses are urgently needed. T cell immunity has an important protective role against IAV, and T cell-based vaccines represent an important new development, worldwide, in efforts to combat influenza (4). Study of IAV-specific T cell immunity has focused more on CD8+ T cells (5, 6) partly due to the lack of accurate prediction algorithms for CD4+ T cell epitopes that often show promiscuous length requirement (7). Specific CD4+ T cell responses were proven to be indispensable

Methods

Results

Conclusion