Scientific Focus
Research Interests
One of our focuses is to define gamma delta T cell function. This type of T cells is one of the least understood components of the immune system. Yet, it is clear that gamma delta T cells contribute uniquely to host immune competence. In some human infections such as HIV, or in early lesions of MS patients, the percentage of gamma delta T cells in the blood, or the brain can increase to be ~50% (as compared to the below 5% in healthy individuals) of the total T cells. In the past, we showed that gamma delta T cell receptors and alpha beta T cell receptors have profound differences in their antigen recognition requirements. While alpha beta TCR recognize peptide/ MHC molecules, gamma delta T cells seem to focus on self-ligands, which act as sensors of physiological disturbance. We have identified a natural ligand for murine gamma delta T cells, the only one that has been identified so far and determined how this repertoire is generated. We want to follow up on these studies to determine other gamma delta T cell ligands, to understand, how self-recognition and subsequent effector functions in infection and autoimmune diseases are regulated.
Another area is on the host response to Yersinia pseudotuberculosis infection. Y. pseudotuberculosis is gram-negative bacteria related to the causative agent of bubonic plague. They can cause enteric diseases, lymphadenitis and septicemia. In addition, mild infection may trigger autoimmune disorders such as thyoiditis and reactive arthritis. We found Yersinia infection efficiently and profoundly inhibits antigen receptor mediated T cell and B cell functions. We currently analyze host responses to this infection and how the infection modulates immune responses to non-Yersinia antigens.
Publications
- Cutting edge: Gammadelta intraepithelial lymphocytes of the small intestine are not biased toward thymic antigens. J Immunol. 2009; (12): 7348-51
- Thymic maturation determines gammadelta T cell function, but not their antigen specificities. Curr Opin Immunol. 2009; (2): 140-5
- An autonomous CDR3delta is sufficient for recognition of the nonclassical MHC class I molecules T10 and T22 by gammadelta T cells. Nat Immunol. 2008; (7): 777-84
- Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma. Immunity. 2008; (1): 90-100
- Antigen recognition by gammadelta T cells. Immunol Rev. 2007: 46-58
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