Microbiology and Immunology Thomas Jefferson University Jefferson Medical College

Laurence C. Eisenlohr, V.M.D., Ph.D.

Department of Microbiology and Immunology
Professor

Mailing Address

BLSB Room 730, 233 S. 10th Street
Philadelphia, Pennsylvania 19107
United States

Contact Information

Phone: 215-503-4540
Fax: 215-923-4153
Laurence.Eisenlohr@mail.jci.tju.edu

Qualifications

V.M.D., University of Pennsylvania, 1983
Ph.D., University of Pennsylvania, Immunology, 1988

Expertise and Research Interests

There are currently five major interests in the Eisenlohr laboratory all of which relate to T cell recognition of antigen.

Processing and presentation for class I-restricted T cell recognition. Most effort is being expended to determine the cellular elements involved in antigen processing and how subcellular location impacts the efficiency of antigen processing. These issues are being addressed through expression of genetically-manipulated influenza proteins bearing known class I-restricted T cell determinants. The approach has provided important information about the proteases that contribute to antigen processing and the efficiency with which proteins and protein fragments traffick within the cell.

Processing and loading compartments involved in presentation of MHC class II-restricted antigenic peptides. We are utilizing two glycoproteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA) 1) to identify the subcellular compartments within the cell where antigen becomes available for binding to class II molecules and the compartments where binding takes place, and 2) to determine the extent to which these processes differ in different cell types and when the antigen is taken up from the extracellular space vs. expressed in the antigen presenting cell itself.

The expression and response to "cryptic" MHC class I-restricted epitopes. MHC class I-restricted cytotoxic T lymphocytes (CTL) are exquisitely sensitive to low levels of antigens and we and others have demonstrated that they can be triggered by the products of aberrant gene expression, such as alternative splicing, exon translation, alternative start codon usage and frameshifting. We hypothesize that these aberrant translation products play an important role in defining the world of "self" and may be involved in triggering autoimmunity. In a collaboration with the laboratory of Dr. Raymond Gesteland (U. of Utah) we are currently focusing on one of these mechanisms, ribosomal frameshifting, and its role in T cell activation.

Dynamics of CD8+ T cell responses. Using tools generated in association with project 1, we are now investigating the impact that antigen dose has upon the magnitude of the T cell response and the character of the resulting memory population.

Thyroid cancer and autoimmunity. We are collaborating with Dr. Jay Rothstein (Department of Otolaryngology-HNS) to determine basis for the link between autoimmune thyroiditis and thyroid neoplasia. Our role in this project has been to design proteins that are expressed in thyroid tissue of transgenic mice that can be used to trigger autoimmune thyroiditis. Depending upon the engineering of these proteins, that impacts the way they are processed for presentation to T cells, we expect the character of the autoimmune response to vary. We anticipate that many of the same approaches taken in this project will apply to a recently-initiated collaboration with Dr. Scott Waldman (Department of Medicine/Director of Clinical Pharmacology) to address similar questions in colon cancer.

Findings related to these five projects will contribute important information to the areas of vaccine design, tissue transplantation, autoimmune therapy, and immune-based anti-cancer strategies.

Keywords

Allergy; Antigen Presentation; Antigen Presenting Cell; Antigen Processing; Chimeric Protein; Confocal Scanning Microscopy; Density Gradient Ultracentrifugation; Endoplasmic Reticulum; Golgi Apparatus; Helper T Lymphocyte; High Performance Liquid Chromatography; Hybridoma; Immunology; Influenza Virus; Influenzavirus A; Intracellular Transport; L Cell; Laboratory Mouse; Lysosome; Mhc Class I Molecules; MHC Class II Antigen; MHC Class II Molecules; Microorganism Hemagglutinin; Protein Degradation; Protein Engineering; Proteolysis; Sialidase; Site Directed Mutagenesis; Tissue Cell Culture; Virus Antigen; Virus Protein

Publications

  • Eisenlohr, L. C., Huang, L. and Golovina, T. N. 2007. Rethinking peptide supply to MHC class I molecules. Nat Rev Immunol, 7:403-410.
  • Plesa, G., McKenna, P.M., Schnell, M.J., and L. C. Eisenlohr, 2006. Immunogenicity of cytopathic and non-cytopathic viral vectors, J. Virol., 80: 6259-6266.
  • Zook, M.B, Howard, M.T., Plesa, G., Atkins, J.F., and L. C. Eisenlohr. 2006. Epitopes derived by incidental translational frameshifting give rise to a protective CTL response, J. Immunol. 176: 6928-6934.
  • Wherry, E.J., Golovina, T.N., Morrison, S.E., Sinnathamby, G., McElhaugh, M.J., Shockey, D.C. and L.C. Eisenlohr. 2006. Re-evaluating the Generation of a Proteasome-Independent MHC Class I-Restricted CD8 T Cell Epitope, J. Immunol. 176:2249-2261.
  • Golovina TN, Morrison SE, Eisenlohr LC. The impact of misfolding versus targeted degradation on the efficiency o the MHC class I-restricted antigen processing. J Immunol 2005 Mar 1;174(5):2763-9.
  • Tewari MK, Sinnathamby G, Rajagopal D, Eisenlohr LC. A cytosolic pathway for MHC class II-restricted antigen processing that is proteasome and TAP dependent. Nat Immunol 2005 Mar;6(3):287-94.
  • Sinnathamby G, Maric M, Cresswell P, Eisenlohr LC. Differential requirements for endosomal reduction in the presentation o two H2-E(d)-restricted epitopes from influenza hemagglutinin. J Immunol 2004 Jun 1;172(11):6607-14.
  • Tatsis N, Sinnathamby G, Eisenlohr LC. Vaccinia virus as a tool for immunologic studies. Methods Mol Biol 2004;269:267-88.
  • Sinnathamby G, Eisenlohr LC. Presentation by recycling MHC class II molecules of an influenza hemagglutinin-derived epitope that is revealed in the early endosome by acidification. Journal of Immunology (baltimore, Md. : 1950). 170(7): 3504-13, Apr 2003
  • Powell DJ Jr, Eisenlohr LC, Rothstein JL. A thyroid tumor-specific antigen formed by the fusion of two self proteins. Journal of Immunology (baltimore, Md. : 1950). 170(2): 861-9, Jan 2003
  • Wherry EJ, McElhaugh MJ, Eisenlohr LC. Generation of CD8(+) T cell memory in response to low, high, and excessive levels of epitope. Journal of Immunology (baltimore, Md. : 1950). 168(9): 4455-61, May 2002
  • Golovina TN, Wherry EJ, Bullock TN, Eisenlohr LC. Efficient and qualitatively distinct MHC class I-restricted presentation of antigen targeted to the endoplasmic reticulum. Journal of Immunology (baltimore, Md. : 1950). 168(6): 2667-75, Mar 2002
  • Wherry EJ, Rajagopal D, Eisenlohr LC. Use of vaccinia virus expression vectors to investigate antigen processing and presentation. Methods in Molecular Biology. 156: 89-109, 2001
  • Wherry EJ; Puorro KA; Porgador A; Eisenlohr LC. The induction of virus-specific CTL as a function of increasing epitope expression: responses rise steadily until excessively high levels of epitope are attained. Journal of Immunology. 163(7): 3735-45, 1 Oct 1999
  • Trotta R, Puorro KA, Paroli M, Azzoni L, Abebe B, Eisenlohr LC, Perussia B. Dependence of both spontaneous and antibody-dependent, granule exocytosis-mediated NK cell cytotoxicity on extracellular signal-regulated kinases. Journal of Immunology. 161(12): 6648-56, 1998
  • Chianese-Bullock KA, Russell HI, Moller C, Gerhard W, Monaco JJ, Eisenlohr LC. Antigen processing of two H2-IEd-restricted epitopes is differentially influenced by the structural changes in a viral glycoprotein. Journal of Immunology. 161(4): 1599-607, 1998
  • Lattime EC, Eisenlohr LC, Gomella LG, Mastrangelo M.J. In Gene Therapy of Cancer: Translational Approaches from Preclinical Studies to Clinical Implementation , eds. Lattime, E. C. & Gerson, S. L. (Academic Press, San Diego). 125-137, 1998
  • Mastrangelo MJ, Maguire HC, Eisenlohr LC, Monken CE, McCue P, Kovatich AJ, Lattime EC. American Association for Cancer Research. 39: 361, 1998
  • Bullock TN, Patterson AE, Franlin LL, Notidis E, Eisenlohr LC. Initiation codon scanthrough versus termination codon readthrough demonstrates strong potential for major histocompatibility complex class I-restricted cryptic epitope expression. Journal of Experimental Medicine. 186(7): 1051-8, 1997
  • Yellen-Shaw AJ, Eisenlohr LC. Regulation of class I-restricted epitope processing by local or distal flanking sequence. Journal of Immunology. 158(4): 1727-33, 1997
  • Yellen-Shaw AJ, Wherry EJ, Dubois GC, Eisenlohr LC. Point mutation flanking a CTL epitope ablates in vitro and in vivo recognition of a full-length viral protein. Journal of Immunology. 158(7): 3227-34, 1997
  • Yellen-Shaw AJ; Laughlin CE; Metrione RM; Eisenlohr LC. Murine transporter associated with antigen presentation \(TAP\) preferences influence class I-restricted T cell responses. Journal of Experimental Medicine. 186(10): 1655-62, 17 Nov 1997

RECENT PRESS

Health experts to address issues in education, research, practice
January 26, 2012--DHSA will hold its inaugural Global Health Symposium on Saturday, Feb. 4 at CCHS. The program will focus on education, research and practice, with presentations on topics ranging from refugee health clinics and relief medicine to anthropological approaches to the study of global health.
Christiana Care issues a call to men to prevent domestic violence
January 24, 2012--Christiana Care, a National Community Center of Excellence in Women's Health, has been working for years to help women who are victims of domestic violence at an annual event that offers resources, education and support.
After Holiday Eating Marathon, Jefferson Dietitian Offers 10 Tips to Get Back on Track and Kick Start New Year's Weight Loss Resolution
January 4, 2012--Celebrating the New Year goes hand-in-hand with creating resolutions to get healthy and trim - especially after weeks of holiday marathon eating. Dietitian Emily Rubin, R.D., L.D., with the Division of Gastroenterology at Thomas Jefferson University Hospital, says you can stay committed to being healthy and fit by following these 10 tips.
Procedure saves teen after rare carotid trauma
January 4, 2012--Neurointerventionalist Gregg Zoarski, M.D.'s recent surgical grand rounds lecture on carotid artery injuries focused on how to repair traumatic injuries to these vital vessels that supply blood to the brain.
Medical students delighted with Delaware branch campus Christiana Care is participating in Jefferson Medical College’s Delaware Branch Campus program, underscoring the transformative role the health system plays in medical education.
December 23, 2011--This achievement specifically spotlights our core competency in providing clinical education to third- and fourth-year medical students. Christiana Care has a long-standing relationship in providing first-rate medical education to students from Jefferson, one of the country's top-rated medical collleges.
Healthy Kids Delaware (HKD) Network celebrated its one-year anniversary earlier this month.
December 22, 2011--Earlier this month the Healthy Kids Delaware (HKD) network celebrated its one-year anniversary. The Healthy Kids Delaware network has been working to address health and wellness needs of children throughout New Castle County.
Interprofessional Care for the 21st Century: Redefining Education and Practice
December 14, 2011--Registration is now open for Jefferson InterProfessional Education Center's (JCIPE) 2012 conference: Interprofessional Care for the 21st Century: Redefining Education and Practice. The conference will be held on May 18-19, 2012 at Dorrance H. Hamilton Building, Thomas Jefferson University, Philadelphia, PA. The purpose of this conference is to showcase scholarly work and works in progress advancing interprofessional education and/or practice. This conference reflects on innovative implementation and evaluation strategies of the interprofessional competencies.
Nemours participates in Partnership for a Healthier America Summit
December 8, 2011--The Partnership, of which Nemours is a founding member, has a mission of supporting First Lady Michelle Obama's Let's Move! campaign by working with the private sector to fight childhood obesity. The theme that emerged at the summit, a gathering of leaders from business and industry, academia, nonprofits and government, was: "Make the healthy choice the easy choice."
DHSA plans workshop on collaborative education for clinicians and scientists
December 8, 2011--DHSA will host "Creating Clinical and Research Teams for the Future: Workshop on Collaborative Education for Clinicians and Scientists" on Tuesday, Jan. 10, 2012, at the Ammon Education Center of Christiana Hospital. This workshop focuses on developing skills to write educational grants. The program will include information on how to obtain educational grant funding, set goals and evaluate an educational program, and develop an application for the DHSA Education Pilot Award.