The research focus of the Kwok Laboratory is the study of antigen specific CD4+ T cells using tetramers. Historically, T cells with known antigen specificity have been difficult to detect and isolate. The use of class II tetramer reagents has provided a more effective approach for studying CD4+ T cell responses. Over the past decade, our research projects have used HLA class II tetramers to probe human CD4+ T cell responses in diverse disease settings.
Specific research emphases include:
1. Class II tetramer production: tetramer reagents for more than 30 different HLA class II alleles are produced through the Tetramer Core Laboratory. These reagents can be used to study human CD4+ T cell responses over a wide cross section of the population. Class II tetramers that can be used for CYTOF mass cytometry are also being produced in the core laboratory.
2. T cell epitope discovery: A robust, generalized approach has been developed and implemented to systematically identify CD4+ T cell epitopes. This approach is applied to identify T cell epitopes within Categories A, B and C pathogens, tumor antigens, allergens and antigens associated with autoimmune diseases in humans.
3. Autoimmune disease: Tetramers are used to examine autoreactive CD4+ T cells in type 1 diabetes and multiple sclerosis. Experiments are designed to determine the molecular mechanisms of HLA and autoimmune disease association. HLA that are linked to disease susceptibility or disease protection have been identified. Contrasting the behavior of T cells restricted by susceptible and protective HLA alleles should provide insights into disease mechanisms and suggest strategies for intervention.
4. Allergy: Tetramers are being applied to examine CD4+ T cell responses to environmental allergens such as dust mites and pollens, and food allergens such as peanut and milk, in non-allergic and allergic subjects. Allergen specific T cell responses are also being monitored during the course of immunotherapy. These studies should aid our understanding of the early stages of allergy development and suggest new strategies for therapy.
5. Infectious pathogens: Tetramers present a novel approach to study T cell responses against pathogens such as seasonal and avian influenza, Dengue, West Niles virus, Japanese Encephalitis virus, Yellow Fever virus and Mycobacterium tuberculosis. Research participants that are exposed to these organisms by either infection or vaccination are recruited. Studies are carried out to characterize antigen specific T cell responses and to dissect the underlying mechanism for the development of long lasting protective immune responses.
6. Antigen specific Immune Responses: Other techniques are also being utilized to examine the collaboration between antigen specific T cell and B cell responses.