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Thomas Jefferson University - Laurence C. Eisenlohr, VMD, PhD
Laurence C. Eisenlohr, VMD, PhD

Microbiology & Immunology
Thomas Jefferson University
Jefferson Medical College
Department of Microbiology and Immunology
Professor

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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
Personal Web Site
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
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Individual Expertise profile of Laurence C. Eisenlohr, VMD, PhD, Copyright © Laurence C. Eisenlohr, VMD, PhD.
Last Updated by Laurence Eisenlohr, VMD, PhD : Thursday, April 3, 2008 4:22:18 PM



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