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A Novel Approach of Identifying Immunodominant Self and Viral Antigen Cross-Reactive T Cells and Defining the Epitopes They Recognize.
- Source :
-
Frontiers in immunology [Front Immunol] 2018 Dec 03; Vol. 9, pp. 2811. Date of Electronic Publication: 2018 Dec 03 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- ADP-ribosyl Cyclase 1 immunology
Amino Acid Sequence
CD4-Positive T-Lymphocytes virology
Diabetes Mellitus, Type 1 immunology
Diabetes Mellitus, Type 1 virology
Glutamate Decarboxylase immunology
HLA-DR Antigens immunology
Humans
Influenza A virus immunology
Influenza Vaccines immunology
Influenza, Human immunology
Peptides immunology
Antigens, Viral immunology
CD4-Positive T-Lymphocytes immunology
Cross Reactions immunology
Epitopes, T-Lymphocyte immunology
Immunodominant Epitopes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30619245
- Full Text :
- https://doi.org/10.3389/fimmu.2018.02811