Clonotype-specific avidity influences the dynamics and hierarchy of virus-specific regulatory and effector CD4(+) T-cell responses.

Abstract

A key component of immunity against viruses, CD4(+) T cells expand and differentiate into functional subsets upon primary infection, where effector (Teff) cells facilitate infection control and regulatory (Treg) cells mitigate immunopathology. After secondary infection, Teff cells mount a robust response from the memory pool. Here, we show that Treg-cell responses are diminished upon secondary infection, and Treg-cell response dynamics are associated more with T-cell receptors (TCRs) repertoire and avidity than with epitope specificity. In the murine model, the IA(b) M209 epitope of respiratory syncytial virus is recognized by both CD4(+) Treg and Teff cells, while the IA(b) M226 epitope is recognized almost exclusively by CD4(+) Teff cells expressing high avidity TCR Vβ8.1/8.2 and dominating the CD4(+) T-cell response during primary and secondary infections. IA(b) M209 -Teff cells express relatively low avidity TCRs during early primary infection, but high avidity TCR Vβ7-expressing IA(b) M209 -Teff cells emerge during the late phase, and become dominant after secondary infection. The emerging high avidity IA(b) M209 -Teff cells outcompete IA(b) M209 -Treg cells that share the same epitope, but have low avidity and are restricted to TCR Vβ2 and Vβ6 subpopulations. These data indicate that MHC-peptide-TCR interactions can produce different kinetic and functional profiles in CD4(+) T-cell populations even when responding to the same epitope.

• Authors: Jie Liu, Shirley Cao, Gretchen Peppers, Sung-Han Kim, Barney S Graham
• Journal: European journal of immunology (Eur J Immunol) Vol. 44 Issue 4 Pg. 1058-68 (Apr 2014) ISSN: 1521-4141 [Electronic] Germany
• PMID: 24510524 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Chemical References

• Epitopes, T-Lymphocyte
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Animals
• Binding, Competitive (immunology)
• CD4-Positive T-Lymphocytes (immunology, metabolism, virology)
• Cell Line, Tumor
• Cell Proliferation
• Cells, Cultured
• Clone Cells (immunology, metabolism, virology)
• Epitopes, T-Lymphocyte (immunology, metabolism)
• Flow Cytometry
• Host-Pathogen Interactions (immunology)
• Humans
• Kinetics
• Mice
• Mice, Inbred C57BL
• Receptors, Antigen, T-Cell, alpha-beta (immunology, metabolism)
• Respiratory Syncytial Virus Infections (immunology, virology)
• Respiratory Syncytial Viruses (immunology, physiology)
• T-Lymphocytes, Regulatory (immunology, metabolism, virology)