Perelman School of Medicine at the University of Pennsylvania

Penn Institute for Immunology

Laura F Su

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Assistant Professor of Medicine
Department: Medicine
Graduate Group Affiliations

Contact information
421 Curie Boulevard
Philadelphia, PA
BS (Biology)
Massachusetts Institute of Technology, Cambridge, MA, 1996.
New York University School of Medicine, New York, NY, 2003.
New York University School of Medicine, New York, NY, 2003.
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Description of Research Expertise

Description of Research Expertise

Research Interests:
The general focus of the lab is on human CD4+ T cell immunity. We are particularly interested in understanding how T cell cross-reactivity and past microbial exposure influence subsequent immune competence and the risk for developing autoimmunity.

CD4+ T cells, memory, cross-reactivity, peptide-MHC tetramers, TCR repertoire, vaccination, autoimmunity, rheumatoid arthritis.

Research summary:
Mouse biology approximate human system in many respects, but there are invariably inter-species differences that make direct study of humans valuable and necessary to fully understand health and disease. One fundamental question is what intrinsic factors and external influences modulate the robustness of an immune response in humans. We still do not understand why some vaccines are more effective than others, why people respond differently, and how prior antigen experiences and environmental exposures impact the risk for developing autoimmunity. My lab is interested in addressing these questions with a focus on human CD4+ T cells. We showed in an earlier study that a large proportion of human CD4+ T cells can acquire memory characteristics indicative of prior exposure even in the absence of known specific contact with the antigen. This for instance was seen in HIV-reactive T cells, which were found in every healthy blood donor we surveyed; we also detected in these HIV negative individuals a prominent memory population recognizing HIV antigen. This conundrum could potentially be explained by the flexibility in ligand recognition by T cell receptors (TCRs), which allow the same T cell to become activated by distinctly different ligands and is referred to as “cross-reactivity”. Consistent with this we found HIV-reactive T cells from HIV negative individuals to recognize many other microbial peptides, including those derived from skin and gut commensal bacteria and microbes in the environment. The absence of these memory phenotype cells in the blood of newborns provides additional support for the likely explanation that pre-existing T cell memory was generated by cross-reactive exposure to common microbes.

The lab focuses on:
1) Understanding the biological relevance of memory phenotype T cells generated by prior cross-reactive exposures. Because a typical memory cell responds faster and more robustly to antigen stimulation than a naïve T cell, cells that have previously acquired a memory phenotype by other means might play a critical role in immune defense by magnifying the response to a novel immune perturbation. We are also interested in how TCR cross-reactivity could influence the magnitude of a response in humans and will explore whether cells bearing more cross-reactive TCRs are preferentially expanded after vaccination.

2) Understanding whether commensal microbes promote self-directed T cell memory and how these memory phenotype T cells contribute to autoimmunity. We are particularly interested in addressing these questions in the context of rheumatoid arthritis (RA), which is a leading cause of disability in the US characterized by systemic inflammation and destructive joint erosions. We are identifying disease relevant autoreactive T cell populations from patients with RA and determining if these cells have aberrant memory and functional characteristics. We are also interested in whether specific autoreactive populations are more cross-reactive, and should they recognize commensal microbes, how microbial stimulation alters their response to self-antigens.

Students are encouraged to contact Dr. Su about potential rotation projects.

Selected Publications

Herati RH, Muselman A, Vella L, Bengsch B, Kotzin J, Del Alcazar D, Parkhouse K, Tebas P, Doyle SA, Hensley S, Su LF, Schmader KE, Wherry J: Successive annual influenza vaccination induces a recurrent oligoclonotypic memory response in circulating T follicular helper cells. Science Immunology 2(3): eaag2152, Febrary 2017.

Su LF, Del Alcazar D, Stelekati E, Wherry EJ, Davis MM: Antigen exposure shapes the ratio between antigen-specific Tregs and conventional T cells in human peripheral blood. PNAS 113(40): E6192-6198, September 2016.

Huang J, Zeng X, Sigal N, Lund PJ, Su LF, Huang H, Chien YH, Davis MM: Detection, phenotyping, and quantification of antigen-specific T cells using a peptide-MHC dodecamer. PNAS 113(13): E1890-1897, March 2016.

Su LF, Han A, McGuire HM, Furman D, Newell EW, Davis MM: The Promised Land of Human Immunology Cold Spring Harbor Symposia on Quantitative Biology Page: 1-11, March 2014.

Su LF, Davis MM: Antiviral memory phenotype T cells in unexposed adults. Immunol Rev. 255(1): 95-109, Sep 2013

Locci M, Havenar-Daughton C, Landais E, Wu J, Kroenke MA, Arlehamn CL, Su LF, Cubas R, Davis MM, Sette A, Haddad EK; International AIDS Vaccine Initiative Protocol C Principal Investigators, Poignard P, Crotty S.: Human circulating PD-⁺1CXCR3⁻CXCR5⁺ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses. Immunity 39((4)): 758-69, Oct 2013.

Su LF, Kidd B, Han A, Kotzin J, Davis MM: "Virus-specific CD4+ memory phenotype T cells are abundant in unexposed adults" Immunity 38(2): 373-383, February 2013.

Wang C, Krishnakumar S, Wilhelmy J, Babrzadeh F, Stepanyan L, Su LF, Levinson D, Fernandez-Vina MA, Davis RW, Davis MM, Mindrinos M.: "High-throughput, high-fidelity HLA genotyping with deep sequencing" PNAS 109(22): 8676-8681, May 2012.

Su LF.: "Predictive Biomarkers – One Step Beyond" Rheumatology Report 5(1), 2011.

Su LF. : "Updates on high-throughput molecular profiling for the study of rheumatoid arthritis" Isr Med Assoc J 10(4): 307-9, April 2008.

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Last updated: 12/10/2017
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