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Research Interests:
T-cell development
My lab is interested in the molecular mechanisms of T lymphocyte
development. One of the interesting issues in this field is
how the T cell receptor interacts with MHC/peptide ligands
to result in either positive selection (life) or negative
selection (death) at a particular stage in development. We
have identified several synthetic and natural peptide ligands
that induce one or the other, and are studying their structure
and ability to initiate biochemical signals through the TCR.
We would like to understand how the receptor transduces apoptotic
signals under conditions of strong ligation, but survival
and differentiation signals under weak ligation. Our current
approaches include flow cytometric and microscopic analysis
of signal transduction in intact organs, gene expression profiling,
and RNAi “knock-down” analysis. We are also interested
in how thymic selection events regulate VDJ recombination.
Specifically, we are testing whether recombinase gene expression
and chromatin accessibility are differently regulated by strong
versus weak TCR signaling. Our results support the intruiging
hypothesis that basal signaling is required to maintain receptor
clonality. Finally, we are interested in how peripheral CD8
T cells that recognize antigens in epithelial tissues are
regulated. It would appear that the specialized antigen presenting
cells for the skin epidermis are not tolerogenic in the normal
state. We would like to understand the molecular basis of
this, and what it means for the regulation of immunity at
barrier surfaces.
Selected Recent Publications:
- REVIEW: Hogquist K.A., Baldwin T.A. and S.C. Jameson. Central Tolerance: Learning Self Control in the Thymus. Nature Reviews Immunology In Press (2005).
- Baldwin, T.A., Sandau, M.M, Jameson, S.C., and K.A. Hogquist. The timing of TCRa expression critically influences T cell development and selection. J. Exp. Med. 202:111 (2005)
- Mick, V.E., Starr, T.K., McCaughtry, T.M., McNeil, L.K., and K.A. Hogquist. The regulated expression of a diverse set of genes during thymocyte positive selection in vivo. J. Immunol. 173:5434 (2004).
- Mayerova, D., Parke, E.A., Bursch, L.S., Odumade, O.A., and K.A. Hogquist. Langerhans cells activate naïve self-antigen specific CD8 T cells in the steady state. Immunity 21:391 (2004).
- D. Mayerova and K.A. Hogquist Central tolerance to self-antigen expressed by cortical epithelial cells. J. Immunol. 172:851 (2004).
- Holman, P.O., Walsh, E.R., and K.A. Hogquist. The central
tolerance response to male antigen in normal mice is clonal
deletion and not receptor editing. J.
Immunol. 171:4048 (2003).
- Starr, T.K., Daniels, M.A., Lucido, M.M., Jameson S.C.,
and K.A. Hogquist. Thymocyte sensitivity and SMAC formation
are developmentally regulated: a role for sialylation. J.
Immunol. 171:4512 (2003)
- Santori, F.R., William C. Kieper, Stuart M. Brown, Yun
Lu, Thomas A. Neubert, Kenneth L. Johnson, Stephen Naylor,
Stanislav Vukmanovic, Kristin A. Hogquist, and Stephen C.
Jameson. Rare, structurally homologous self-peptides promote
thymocyte positive selection. Immunity
17:131-42 (2002).
- McGargill, M.A., Mayerova, D., Stefanski, H.E., Koehn, B., Parke, E.A., Jameson S.C., Panoskaltsis-Mortari, A., and K.A. Hogquist. A spontaneous CD8 T cell dependent autoimmune disease to an antigen expressed under the K14 promoter. J. Immunol. 169(4):2141-7 (2002).
Last modified on: October 3, 2005
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