Kristin A. Hogquist, Ph.D.
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
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
Selected Recent Publications:
- Lee YJ, Holzapfel KL, Zhu J, Jameson SC, and KA Hogquist. 2013. Steady state production of IL-4 modulates immunity in different strains and is determined by lineage diversity of iNKT cells. Nature Immunology 14:1146.
- Xing Y, Jameson SC, and KA Hogquist. 2013. The thymoproteasome subunit β5T generates pMHC specialized for positive selection. Proc Natl Acad Sci U S A. 110:6979.
- Stritesky GL, Xing Y, Erickson JR, Kalekar LA, Mueller DM, Jameson SC, and KA Hogquist. 2013. Murine thymic selection quantified using a novel method to capture deleted T cells. Proc Natl Acad Sci U S A. 110:4679.
- Balfour, HH, Odumade, O.A. Schmeling, D.O., Mullan, BD, Ed, JA, Knight, JA, Vezina, HE, Thomas, W and KA Hogquist. 2013. Virologic, and Immunologic Factors Associated with Acquisition and Severity of Primary Epstein-Barr Virus Infection in University Students. J. Inf. Dis. 207(01):80-8.
- REVIEW: Stritesky GL, Jameson SC, Hogquist KA. 2012. Selection of self-reactive T cells in the thymus. Annu Rev Immunol. 30:95.
- Odumade, O.A., Knight, J.A., Schmeling, D.O., Masopust D., Balfour, H.H. Jr., and K.A. Hogquist. 2012. Primary Epstein-Barr virus infection does not erode pre-existing CD8 T cell memory in humans. J. Exp. Med. 209:471.
- Moran, A.E., Holzapfel K.L. Xing, Y., Cunningham, N.R., Maltzman, J.S., Punt, J., and K.A. Hogquist. 2011. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J. Exp. Med. 208:1279.
- REVIEW: Lee, Y.J., Jameson, S.C., and K.A. Hogquist. 2011. Alternative memory in the CD8 lineage. Trends in Immunology 32:50.
- Weinreich, M.A., Jameson S.C., and K.A. Hogquist. 2011. Post- selection thymocyte maturation and emigration are independent of IL-7 and ERK5. J Immunol. 186:1343.
- REVIEW: Odumade, O.A., Hogquist, K.A., and H. J. Balfour III. 2011. Progress and Problems in Understanding and Managing Epstein-Barr Virus Infections. Clin Microbiol Rev 24:193.
- Weinreich, M.A., Odumade, O.A., Jameson S.C., and K.A. Hogquist. 2010. PLZF+ T cells regulate memory-like CD8 T cell development. Nature Immunology, 11:709.
- Odumade, O.A., Weinreich M.A., Jameson S.C., and K.A. Hogquist. 2010. Kruppel-like factor 2 regulates trafficking and homeostasis of gammadelta T cells. J. Immunol. 184:6060.
- Wang L., Jameson, S.C., and K.A. Hogquist. 2009. Epidermal Langerhans cells are not required for UV induced immunosuppression. J. Immunol. 183:5548.
- 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,
- 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.
- 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.