Immunology Research



T cells play a critical role in protection from inf
ectious disease as they recognize and respond to pathogen specific epitopes. After an infection antigen specific T cells dramatically expand, contract, and become short-lived effector cells or are maintained as long-lived memory cells that rapidly respond to a additional challenges. Helper T cells play a central role in the coordination of the adaptive and innate immune responses and deliver essential survival signals for the generation of cytotoxic memory T cells, antibody responses, and protective immunity. A better understanding of T cell activation and memory formation provides an opportunity to effectively improve vaccines and protection from infectious disease.


The main areas of research in the Weber lab are:

1)
Improving T cell memory response to infectious disease 2) Understanding the molecular basis of T cell and macrophage activation 3) Engineering improved immunological proteins helpful in combating disease
and 4) Understanding how dust mite exposure influences the immune system and development of asthma.

  Lab "Korean pants" day.




Improving T cell memory response to infectious disease

Our lab is focused on understanding the signals for proper development and function of CD4 T cell memory. We have generated two CD4 T cell receptor transgenic mice specific for the same naturally occurring epitope from Listeria monocytogenes. These transgenic mice, called LLO118 and LLO56, have dramatically different primary and secondary responses to infection.  LLO118 has a strong primary response relative to LLO56, whereas LLO56 has a much better memory response compared to LLO118. Understanding why these dramatic differences between primary and secondary responses exist could provide important insights into why some T cells are better at providing immunity to infection and generating memory cells and how this can be improved.





 Understanding the molecular basis of T cell and macrophage activation

A second focus of the lab is to understand the molecular and cellular basis of T cell and macrophage activation. We are examining this using live cell calcium imaging of T cells as they interact with antigen presenting cells. This allows us to visualize T cell and macrophage activation real time and determine how different conditions alter T cell and macrophage function. This data will provide insights into T cell and macrophage subtypes and why they respond so differently to one another in infectious disease and cancer settings.





Engineering immunological proteins with improved function


 
A third focus of the lab is engineering immunological proteins with improved function. We are working to understand how high affinity T cell receptors differ in their ability to recognize antigen and cause T cell activation. High affinity T cell receptors are engineered using yeast display and directed evolution and are a novel tool for targeting T cell epitopes not recognized by antibodies. High affinity T cells may be useful as therapeutics in an infectious disease or cancer setting when coupled with pro-inflammatory cytokines or in autoimmunity when coupled with anti-inflammatory cytokines.
 

Examining environmental exposure and asthma and allergy development


A fourth focus of the lab is measuring the role of humidity on dust mite and endotoxin exposure and asthma development.  These measurements are done in homes with swamp coolers or central air conditioning using ELISA to measure levels of dust mite antigens (DerP1/DerF1) and the Limulus Amebocyte Lysate (LAL) test to measure endotoxins.  We are also interested in examining the effects of dust mite and endotoxin exposure on asthma in young children. For more information on our recent publication see the BYU article and video or the FOX news story.