A Novel Approach of Identifying Immunodominant Self and Viral Antigen Cross-Reactive T Cells and Defining the Epitopes They Recognize

Frontiers in Immunology

John A. Gebe¹  Junbao Yang¹  Eddie A. James¹  Lichen Jing²  William W. Kwok²  David M. Koelle³ 

[1] Benaroya Research Institute at Virginia Mason, Seattle, WA, United States;Department of Medicine, University of Washington, Seattle, WA, United States;Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States;

关键词: molecular mimicry;    T cell cross-reactivity;    influenza;    glutamate decarboxylase 65;    autoreactive T cells;   

DOI  :  10.3389/fimmu.2018.02811

来源: DOAJ

【 摘 要 】

Infection and vaccination can lead to activation of autoreactive T cells, including the activation of cross-reactive T cells. However, detecting these cross-reactive T cells and identifying the non-self and self-antigen epitopes is difficult. The current study demonstrates the utility of a novel approach that effectively accomplishes both. We utilized surface expression of CD38 on newly activated CD4 memory T cells as a strategy to identify type 1 diabetes associated autoreactive T cells activated by influenza vaccination in healthy subjects. We identified an influenza A matrix protein (MP) specific CD4+ T cell clone that cross-recognizes an immunodominant epitope from Glutamic Acid Decarboxylase 65 (GAD65) protein. The sequences of the MP and GAD65 peptides are rather distinct, with only 2 identical amino acids within the HLA-DR binding region. This result suggests that activation of autoreactive T cells by microbial infection under certain physiological conditions can occur amongst peptides with minimum amino acid sequence homology. This novel strategy also provides a new research pathway in which to examine activation of autoreactive CD4+ T cells after vaccination or natural infection.

【 授权许可】

Unknown