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Research Interests:
Regulation of T lymphocyte survival, development and activation
by the T cell receptor and by cytokines.
My lab is interested in how T cells develop and are maintained
in the body in a state of readiness to respond to foreign
antigens. It is becoming clear that low affinity interactions
of the T cell receptor (TCR) with self peptide/MHC ligands
is important for all of these processes. How the TCR interaction
with self is kept in check to allow for normal T cell homeostasis
but not to induce autoreactivity is a key question we are
trying to address. In addition, we want to understand how
different self peptide/MHC ligands and cytokines regulate
T cell homeostasis to maintain a useful T cell repertoire.
Finally we are tying in the regulation of T cell homeostasis
to the expression of a transcription factor (called LKLF or KLF2) which was thought to be important for naive T cell maintenance, but that we have recently shown is essential for normal thymocyte and T cell trafficking.
In other work we are testing the nature and consequences
of TCR interaction with low affinity peptide/MHC ligands.
Using multivalent forms of these peptide/MHC ligands (tetramers),
we are dissecting the contribution of both the TCR and its
co-receptor CD8 in ligand binding and correlating this to
the ligand's ability to induce various T cell responses. We
have shown that some low affinity TCR ligands can induce T
cell activation like high affinity ligands, but with drastically
slower activation kinetics and greatly altered patterns of
early signaling events. More recently, we've been studying
regulation of CD8-Class I MHC binding during T cell development
and activation.
Techniques
Cellular immunology assays (e.g. T cell activation assays,
flow cytometric analysis, fetal thymic organ culture assays)
and molecular biology techniques (e.g. real time RT-PCR, western
blot, generation of transgenic mice) are used extensively
in this research.
Selected Recent Publications:
- Carlson C.M., Endrizzi B.T., Wu J., Ding X., Weinreich M.A., Walsh E.R., Wani M.A., Lingrel J.B., Hogquist K.A., Jameson S.C. 2006. Kruppel-like factor 2 regulates thymocyte and T-cell migration. Nature. 442:299-302.
- Kao C., Sandau M.M., Daniels M.A., Jameson S.C. 2006. The sialyltransferase ST3Gal-I is not required for regulation of CD8-class I MHC binding during T cell development. J Immunol. 176:7421-7430.
- Hamilton S.E., Wolkers M.C., Schoenberger S.P., Jameson S.C. 2006. The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cells. Nat Immunol. 7:475-481.
- Holman P.O., Walsh E.R., S.C. Jameson. 2005. Characterizing the impact of CD8 antibodies on class I MHC multimer binding. J Immunol. 174:3986-3991.
- Sandau M.M., Schluns K.S., Lefrancois L., S.C. Jameson. 2004. Cutting edge: transpresentation of IL-15 by bone marrow-derived cells necessitates expression of IL-15 and IL-15R alpha by the same cells. J Immunol. 173:6537-6541.
- Endrizzi, B.T., S.C. Jameson. 2003. Maintenance of LKLF (KLF2) in naïve T cells is independent of IL-7 induced survival. Int. Immunol. 15:1341-1348.
- Prlic M., B. R. Blazar, M. A. Farrar, and S.C. Jameson. 2003. In vivo survival and homeostatic proliferation of NK cells. J.Exp.Med. 197:967.
- Santori F.R., W.C. Kieper, S.M. Brown, Y. Lu., T.A. Neubert, K.L. Johnson, S. Naylor, S. Vukmanovic, K.A. Hogquist, and S.C. Jameson. 2002. Rare, structurally homologous self-peptides promote thymocyte positive selection. Immunity 17:131-142.
- Kieper, W. C., M. Prlic, C. S. Schmidt, M.F. Mescher and
S.C. Jameson. (2001) IL-12 enhances CD8 T cell homeostatic
expansion. J.
Immunol. 166:5515-5521.
- Rosette, C., G. Werlen, M. A. Daniels, P.O. Holman, S.
M. Alam, P.J. Travers, N.R.J. Gascoigne, E. Palmer and S.C.
Jameson. (2001) The impact of duration versus extent of
TCR occupancy on T cell activation: A revision of the kinetic
proofreading model. Immunity
15:59-70 .
- Prlic, M., B. R. Blazar, A. Khoruts, T. Zell and S.C.
Jameson. (2001) Homeostatic expansion occurs independently
of costimulatory signals J.Immunol.
167:5664-5668.
- Daniels, M. A., L. Devine, J. D. Miller, J. M. Moser,
A. E. Lukacher, J. D. Altman, P. Kavathas, K. A. Hogquist,
and S.C. Jameson. 2001. CD8 binding to MHC Class I molecules
is influenced by T cell maturation and glycosylation. Immunity
15:1051-1061.
- Daniels, M.A. and S.C. Jameson. (2000) Critical role for CD8 in TCR binding and activation by peptide/MHC multimers. J. Exp.Med. 191:335-345.
Last modified on:
Tuesday, August 22, 2006 9:14 AM
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