Gamma/delta T cells are one of the least understood components of the immune system. While these cells appear to contribute uniquely to host immune competence, it has been difficult to define their function in the context of host biology or pathology. This is largely because it is unclear what the gamma/delta T cell repertoire is directed against. Previously, we have identified T10/T22 as natural ligands of gamma/delta T cells. Based on the analysis of this system, we postulate that classical and other non-classical MHC molecules, which are induced or otherwise regulated during immune responses, are biologically important gamma/delta T cell ligands. To test this, we have surveyed mice with tetramers of classical and non-classical MHC molecules. Our preliminary results show that sizable populations ofgamma/delta T cells can be identified with the class II MHC, I-Ek, and the non-classical MHCs, CD1d and Qa-1. This suggests that considerable fraction of the gamma/delta TCR repertoire is specific for MHC or MHC-like molecules. Moreover, while the peptides bound to I-E k may not be important for the specificity of recognition, glycolipids bound to CD1d and peptides bound to Qa-1 seem to dominate the specificity. We will extend these studies to include surveys with more sensitive liposomal staining reagents and to analyze the nature of ligand recognition by these specific gamma/delta T cells. Our goal is to gain a better understanding of the gamma/delta TCR repertoire, the manner in which it is regulated and the role of these specificities in the larger context of an immune response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI062794-02
Application #
6986206
Study Section
Cellular and Molecular Immunology - B (CMI)
Program Officer
Winter, David B
Project Start
2004-12-01
Project End
2009-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
2
Fiscal Year
2006
Total Cost
$380,993
Indirect Cost
Name
Stanford University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Chien, Yueh-hsiu; Zeng, Xun; Prinz, Immo (2013) The natural and the inducible: interleukin (IL)-17-producing ýýýý T cells. Trends Immunol 34:151-4
Meyer, Christina; Zeng, Xun; Chien, Yueh-Hsiu (2010) Ligand recognition during thymic development and gammadelta T cell function specification. Semin Immunol 22:207-13
Jensen, Kirk D C; Chien, Yueh-Hsiu (2009) Thymic maturation determines gammadelta T cell function, but not their antigen specificities. Curr Opin Immunol 21:140-5
Jensen, Kirk D C; Shin, Sunny; Chien, Yueh-Hsiu (2009) Cutting edge: Gammadelta intraepithelial lymphocytes of the small intestine are not biased toward thymic antigens. J Immunol 182:7348-51
Konigshofer, Yves; Chien, Yueh-hsiu (2006) Gammadelta T cells - innate immune lymphocytes? Curr Opin Immunol 18:527-33