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Research Interests:
My lab is primarily interested in T cell development in the
thymus. We study how selection processes shape the T cell
repertoire to achieve a highly effective and self-tolerant
adaptive immune system. Current research is focused on these
four topics:
Positive selection: This is a crucial stage
in T cell development, where MHC restricted progenitors are
selected from a random pool. We are systematically studying
the gene changes that occur in the T cell progenitor during
positive selection and how they support the multiple facets
of this event (e.g. survival, migration, allelic exclusion,
etc). We are also exploring how cortical epithelial cells
support the process of positive selection
Negative selection: One of the ways the
immune system copes with self-reactive T cells is to eliminate
them from the repertoire. We developed a highly physiologic
in vivo mouse model to study the specific antigen
presenting cell types involved and the timing and anatomic
location of negative selection. We are also exploring why
some self- reactive cells undergo apoptosis, but others are
selected to become regulatory T cells or NKT 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 to the periphery.
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. Recent studies have focused
heavily on the transcription factor KLF2.
The Human T cell repertoire: We have a unique
collaboration with a clinical virology group to study immune
responses in humans that are at high risk for natural infection
with a gamma herpesvirus (Epstein Barr Virus or EBV). In addition
to documenting the precise changes that occur during the innate
and adaptive immune response to this virus, we are exploring
how the pre-immune T cell repertoire in such individuals is
predisposed to make a pathologic response to this virus (infectious
mononucleosis).
Selected Recent Publications:
- Weinreich, M.A., Takada K., Skon, C., Reiner, S.L., Jameson,
S.C., and K. A. Hogquist. 2009. KLF2 deficiency in T cells
results in unrestrained cytokine production and bystander
chemokine receptor upregulation.Immunity,
31:122.
- Bursch, L.S., Rich, B.E., and K.A. Hogquist. 2009. Langerhans
cells are not required for the CD8 T cell response to epidermal
self antigen. J.
Immunol. 182:4657.
- McCaughtry T.M., Baldwin T.A., Wilken M.S., and K.A. Hogquist.
2008. Clonal deletion of thymocytes can occur in the cortex
with no involvement of the medulla. J.Exp.
Med 205:2575.
- Wang, L., Bursch, L.S., Kissenpfennig, A., Malissen, B.,
Jameson, S.C., and K.A. Hogquist.2008. Langerin expressing
cells promote skin immune responses under defined conditions.
J.
Immunol. 180:4722.
- Bursch, L.S., Wang, L., Igyarto, B., Kissenpfennig, A.,
Malissen, B., Kaplan, D.H., and K.A. Hogquist 2007. Identification
of a novel population of Langerhans cells, J.
Exp. Med. 204:3147.
- Baldwin T.A. and K.A. Hogquist. 2007. Transcriptional
analysis of clonal deletion in vivo. J.
Immunol. 179:837.
- Carlson, C.M., Endrizzi, B.T., Ding, X., Weinreich, M.,
Walsh, E.R., Wu, J., Wani, M.A., Lingrel, J.B., Hogquist,
K.A., and S.C. Jameson. 2006. Lung Kruppel-like factor (KLF2)
regulates thymocyte and T cell migration. Nature
442:299.
- Mayerova, D, Wang, L., and K. A. Hogquist. 2005. Conditioning
of Langerhans cells induced by a primary CD8 T cell response
to self-antigen in vivo. J.
Immunol. 176:4658.
- McNeil, L.K., Starr, T.K., and K. A. Hogquist. 2005. A
requirement for sustained ERK signaling during thymocyte
positive selection in vivo. Proc.
Natl. Acad. Sci.
102:13574.
- Baldwin, T.A., Sandau, M.M, Jameson, S.C., and K.A.
Hogquist. 2005. The timing of TCRa expression critically
influences T cell development and selection. J.
Exp. Med.
202:111.
- Mick, V.E., Starr, T.K., McCaughtry, T.M., McNeil, L.K.,
and K.A. Hogquist. 2004. The regulated expression of a diverse
set of genes during thymocyte positive selection in
vivo. J.
Immunol.
173:5434.
- Mayerova, D., Parke, E.A., Bursch, L.S., Odumade, O.A.,
and K.A. Hogquist.2004. Langerhans cells activate naïve
self-antigen specific CD8 T cells in the steady state.
Immunity
21:391.
- D. Mayerova and K.A. Hogquist. 2004. Central tolerance
to self-antigen expressed by cortical epithelial cells.
J.
Immunol.
172:851.
Last modified on: August 11, 2009
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