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Current Research

Dr. Kristin Hogquist

The primary research interest of the Hogquist lab is T cell development in the thymus. In general, we study how selection processes shape the T cell repertoire to achieve a highly effective, yet self-tolerant, adaptive immune system. Current research is focussed on these four topics:

Positive selection: Only T cell progenitors with appropriate capability to interact with MHC molecules survive T cell development in the thymus. Our lab was one of the first to show that when T cell progenitors in the thymus recognize specific self-peptides with a low affinity this triggers survival and differentiation. We are trying to understand how the cell discriminates between receptor ligand interactions of low versus high affinity, ultimately leading to dramatically distinct signaling and cell fate. We are systematically studying the gene changes that occur during positive selection and how they support the multiple facets of this event (e.g. survival, migration, allelic exclusion, etc).

Negative selection: One of the ways the immune system copes with self-reactive T cells is to eliminate them from the repertoire. We have worked to develop a highly physiologic in vivo model to study this process of negative selection. This model is currently being used to define the specific antigen presenting cell types involved, the timing and anatomic location, and the gene changes that promote apoptosis. We're also interested in exploring why some self- reactive cells undergo apoptosis, but others are selected to become regulatory T cells.

Thymic Emigration: The lab is currently interested in the final stages of maturation that occur prior to migration of the progenitor from the thymus--site of development--to the periphery, where it will participate in immune response. We seek to understand how the functional competence of the cell is eventually switched from apoptosis to proliferation, and the signals, molecular factors, and anatomic structures involved in emigration itself.

Epidermal Langerhans Cells. Yes, this is the odd one out! We are interested in a specialized subset of dendritic cells that reside at epithelial barrier surfaces, and how they contribute to immune responses. Basic studies of antigen processing, presentation, and T cell activation are ongoing. We are developing model systems to study if and how LC contribute to immunological tolerance to epidermal self antigens. Other current work seeks to optimize the means of activating LC, for purposes of needless vaccines (epicutaneous vaccination).

Dr. Stephen Jameson

My lab is interested in the factors which regulate survival and activation of mature T cells. T cells require interactions with self peptide/MHC molecules and with cytokines to develop in the thymus and it is becoming clear that similar interactions are also important in supporting proper homeostasis of the mature T cell pool. In fact, in lymphopenic animals (where there is a deficit in normal T cell numbers), T cells respond to self peptide/MHC ligands and certain cytokines through proliferation and differentiation from naïve into memory T cells. These finding raise the question of how mature T cells control their response to self peptide/MHC so they don’t become overtly autoreactive. We’re characterizing the way in which mature and immature T cells perceive self ligands (and other ligands which bind the TCR with low affinity), and how these signals, together with cytokine signals, influences T cell differentiation and survival. One component of this work is to study a transcription factor, LKLF (KLF-2) which is essential for mature T cell survival. Another aspect is to study how both the TCR and the coreceptor CD8 co-operate in recognition of MHC ligands, using Class I MHC tetramers. We're also testing how competition between T cell subsets (and with NK cells) influences the composition of the lymphoid pool. Finally, we’re interested in how glycosylation influences T cell survival and sensitivity.