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System-wide Analysis of the T Cell Response
Ruxandra Covacu1, Hagit Philip2, Merja Jaronen1
1Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Cell Reports
|March 15, 2016
Summary
Public T cell receptor (TCR) clones in zebrafish dominate immune responses, enabling a limited TCR repertoire to handle diverse antigens. This suggests a rapid T cell immunity mechanism in vertebrates.
Area of Science:
- Immunology
- Comparative genomics
- Vertebrate adaptive immunity
Background:
- The T cell receptor (TCR) orchestrates adaptive immunity against antigens, but its repertoire diversity and response dynamics remain incompletely understood.
- Public TCR clones, shared across individuals with minimal germline alterations, are found in vertebrates, yet their functional significance is unclear.
Purpose of the Study:
- To investigate the zebrafish TCR repertoire and its response to self and foreign antigens.
- To elucidate the role of public TCR clones in adaptive immunity.
Main Methods:
- Analysis of the zebrafish TCR repertoire.
- Antigenic stimulation assays using self and foreign antigens.
- Comparative analysis of TCR clone publicness and cross-reactivity.
Main Results:
- Cross-reactive public TCRs were found to be dominant in the zebrafish T cell response.
- A limited TCR repertoire, through public clones, can effectively address diverse antigenic challenges.
- Zebrafish TCR repertoire exhibits similarities to mammalian systems despite size differences.
Conclusions:
- Public TCRs are crucial for vertebrate adaptive immunity, enabling broad antigen recognition with a limited receptor repertoire.
- These findings suggest a mechanism for rapid T cell immunity generation, potentially allowing subsequent development of private T cell responses.
