Dr. Sara Hamilton

Center for Immunology
Department of Lab Medicine & Pathology
University of Minnesota
MMC 334
420 Delaware St SE
Minneapolis, MN 55406

Lab: 612/625-1626
Fax: 612/625-2199

email: hamil062@umn.edu

Positions

Research Associate (2008– present)
Laboratory of Dr. Stephen Jameson
Department of Lab Medicine & Pathology
University of Minnesota

Postdoctoral Research Associate (2003– 2008)
Laboratory of Dr. Stephen Jameson
Department of Lab Medicine & Pathology
University of Minnesota

Education

Ph.D., University of Iowa, 5/03

B.A., Knox College, 6/98

Current Research

CD8+ T cells with memory-like qualities are generated during lymphopenia-driven homeostatic proliferation (HP). My work has shown that HP-memory T cells display phenotypic and functional characteristics of antigen-experienced memory cells and effectively control pathogens. Furthermore, functional proficiency by HP memory CD8+ T cells requires the presence of CD4 + T cells during the lymphopenia-driven HP phase. It is unknown how CD4+ T cell help is being delivered.
Since CD40-CD40L interactions can play a role in the development of optimal antigen-driven memory, my current research is focused on examining HP cells in an environment where this interaction is prevented. Proliferation and phenotypic changes of CD8+ OT-1 T cells occur as expected in CD40-/- mice. However, these cells were unable to provide protection against high dose challenge with Listeria monocytogenes. In addition, treatment of MHC class II-/- mice with a CD40 agonist antibody during the HP phase overcame the need for CD4+ T cell help.
Thus far, we conclude that CD40 signaling is critical for the development of protective HP memory T cells. My work further suggests that this signal is provided by CD40L on CD4+ T cells and points to an important role for dendritic cells in the delivery of help. Ongoing experiments will dissect the pathway by which HP-memory CD8+ T cells receive the signals that allow them to effectively control pathogens.

Publications

2009

The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion. 2009 Haluszczak C, Akue AD, Hamilton SE, Johnson LD, Pujanauski L, Teodorovic L, Jameson SC, Kedl RM. J Exp Med. Feb 16;206(2):435-448.

Different T cell receptor signals determine CD8+ memory versus effector development.2009 Teixeiro E, Daniels MA, Hamilton SE, Schrum AG, Bragado R, Jameson SC, Palmer E. Science. Jan 23;323(5913):502-5.

2008

The nature of the lymphopenic environment dictates protective function of homeostatic-memory CD8+ T cells. 2008 Hamilton SE, Jameson SC. Proc Natl Acad Sci U S A. Nov 25;105(47):18484-9.

2007

2006

The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cells. 2006. Hamilton, S.E., Wolkers, M. C., Schoenberger, S. P., and S. C. Jameson. Nature Immunology. 7: 475-481.

2004

Environmental conservation: bystander CD4 T cells keep CD8 memories fresh 2004 Hamilton, S. E., Prlic, M., Jameson, S. C. Nat Immunol 5:873-4

Publications not associated with Hogquist - Jameson lab

Listeriolysin O Deficient Listeria monocytogenes as a Vaccine Delivery Vehicle: Antigen-specific CD8 T Cell Priming and Protective Immunity. 2006. Hamilton, S.E., Badovinac, V. P., Khanolkar, A., and J. T. Harty. J. Immunol. 177(6):4012-20.

MHC class Ia-restricted memory T cells inhibit expansion of a nonprotective MHC class Ib (H2-M3)-restricted memory response. 2004 Hamilton S.E., Porter B.B., Messingham K.A., Badovinac V.P., Harty J.T. Nat Immunol 2:159-68

Neutrophil involvement in cross-priming CD8+ T cell responses to bacterial antigens. 2004 Tvinnereim A.R., Hamilton S.E., Harty J.T. J Immunol 173:1994-2002

Badovinac VP, Messingham KA, Hamilton SE, Harty JT. Regulation of CD8+ T cells undergoing primary and secondary responses to infection in the same host. J Immunol. 2003 May 15;170(10):4933-42.

Badovinac VP, Hamilton SE, Harty JT. Viral infection results in massive CD8+ T cell expansion and mortality in vaccinated perforin-deficient mice. Immunity. 2003 Apr;18(4):463-74.

Hamilton SE, Harty JT. Quantitation of CD8+ T cell expansion, memory, and protective immunity after immunization with peptide-coated dendritic cells. J Immunol. 2002 Nov 1;169(9):4936-44.

Tvinnereim AR, Hamilton SE, Harty JT. CD8(+)-T-cell response to secreted and nonsecreted antigens delivered by recombinant Listeria monocytogenes during secondary infection.
Infect Immun. 2002 Jan;70(1):153-62.

Hamilton SE, Tvinnereim AR, Harty JT. Listeria monocytogenes infection overcomes the requirement for CD40 ligand in exogenous antigen presentation to CD8(+) T cells. J Immunol. 2001 Nov 15;167(10):5603-9.

Grandea AG 3rd, Golovina TN, Hamilton SE, Sriram V, Spies T, Brutkiewicz RR, Harty JT, Eisenlohr LC, Van Kaer L. Impaired assembly yet normal trafficking of MHC class I molecules in Tapasin mutant mice. Immunity. 2000 Aug;13(2):213-22.