Photo of Ellis L. Reinherz,  MD

Ellis L. Reinherz, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3412
Fax: (617) 632-3351


ellis_reinherz@dfci.harvard.edu

Ellis L. Reinherz, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Chief, Laboratory of Immunobiology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Laboratory of Immunobiology continues to focus on T lymphocyte recognition of antigen as well as the process of T cell activation and differentiation. Particular emphasis has been placed on studying the structure-function relationship of the T cell receptor (TCR) for antigen in major histocompatibility complex (MHC) products (CD3-Ti), CD2 and CD4. A multi-disciplinary approach involving x-ray crystallography and NMR technologies as well as cellular immunology and molecuar biology is employed.

Publications

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  • Mallis RJ, Bai K, Arthanari H, Hussey RE, Handley M, Li Z, Chingozha L, Duke-Cohan JS, Lu H, Wang JH, Zhu C, Wagner G, Reinherz EL. Pre-TCR ligand binding impacts thymocyte development before 留硫TCR expression. Proc Natl Acad Sci U S A 2015; 112:8373-8. PubMed
  • Reinherz EL. 留硫 TCR-Mediated Recognition: Relevance to Tumor-Antigen Discovery and Cancer Immunotherapy. Cancer Immunol Res 2015; 3:305-312. PubMed
  • Reinherz EL, Wang JH. Codification of bidentate pMHC interaction with TCR and its co-receptor. Trends Immunol 2015. PubMed
  • Hanson MC, Abraham W, Crespo MP, Chen SH, Liu H, Szeto GL, Kim M, Reinherz EL, Irvine DJ. Liposomal vaccines incorporating molecular adjuvants and intrastructural T-cell help promote the immunogenicity of HIV membrane-proximal external region peptides. Vaccine 2015; 33:861-8. PubMed
  • Das DK, Feng Y, Mallis RJ, Li X, Keskin DB, Hussey RE, Brady SK, Wang JH, Wagner G, Reinherz EL, Lang MJ. Force-dependent transition in the T-cell receptor 硫-subunit allosterically regulates peptide discrimination and pMHC bond lifetime. Proc Natl Acad Sci U S A 2015; 112:1517-22. PubMed
  • Yi T, Zhai B, Yu Y, Kiyotsugu Y, Raschle T, Etzkorn M, Seo HC, Nagiec M, Luna RE, Reinherz EL, Blenis J, Gygi SP, Wagner G. Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells. Proc Natl Acad Sci U S A 2014; 111:E2182-90. PubMed
  • Brazin KN, Mallis RJ, Li C, Keskin DB, Arthanari H, Gao Y, Wu SL, Karger BL, Wagner G, Reinherz EL. Constitutively oxidized CxxC motifs within the CD3 heterodimeric ectodomains of the T cell receptor complex enforce the conformation of juxtaposed segments. J Biol Chem 2014. PubMed
  • Choi YI, Duke-Cohan JS, Chen W, Liu B, Rossy J, Tabarin T, Ju L, Gui J, Gaus K, Zhu C, Reinherz EL. Dynamic control of 硫1 integrin adhesion by the plexinD1-sema3E axis. Proc Natl Acad Sci U S A 2014; 111:379-84. PubMed
  • Zhang GL, Riemer AB, Keskin DB, Chitkushev L, Reinherz EL, Brusic V. HPVdb: a data mining system for knowledge discovery in human papillomavirus with applications in T cell immunology and vaccinology. Database (Oxford) 2014; 2014:bau031. PubMed
  • Reinherz EL, Keskin DB, Reinhold B. Forward Vaccinology: CTL Targeting Based upon Physical Detection of HLA-Bound Peptides. 2014; 5:418. PubMed
  • Zhang GL, Keskin DB, Lin HN, Lin HH, DeLuca DS, Leppanen S, Milford EL, Reinherz EL, Brusic V. Human leukocyte antigen typing using a knowledge base coupled with a high-throughput oligonucleotide probe array analysis. 2014; 5:597. PubMed
  • Reinherz EL. Revisiting the Discovery of the 留硫 TCR Complex and Its Co-Receptors. 2014; 5:583. PubMed
  • Olsen LR, Kudahl UJ, Simon C, Sun J, Schönbach C, Reinherz EL, Zhang GL, Brusic V. BlockLogo: visualization of peptide and sequence motif conservation. J Immunol Methods 2013; 400-401:37-44. PubMed
  • Kang YJ, Zeng W, Song W, Reinhold B, Choi J, Brusic V, Yamashita T, Munshi A, Li C, Minvielle S, Anderson KC, Munshi N, Reinherz EL, Sasada T. Identification of human leucocyte antigen (HLA)-A*0201-restricted cytotoxic T lymphocyte epitopes derived from HLA-DO硫 as a novel target for multiple myeloma. British Journal of Haematology 2013; 163:343-51. PubMed
  • Wang JH, Reinherz EL. Revisiting the putative TCR C留 dimerization model through structural analysis. 2013; 4:16. PubMed
  • Choi YI, Duke-Cohan JS, Tan J, Gui J, Singh MK, Epstein JA, Reinherz EL. Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology. 2013; 4:392. PubMed
  • Li XL, Teng MK, Reinherz EL, Wang JH. Strict Major Histocompatibility Complex Molecule Class-Specific Binding by Co-Receptors Enforces MHC-Restricted ホアホイ窶欝CR Recognition during T Lineage Subset Commitment. 2013; 4:383. PubMed
  • Wang JH, Reinherz EL. The structural basis of 留硫 T-lineage immune recognition: TCR docking topologies, mechanotransduction, and co-receptor function. Immunol Rev 2012; 250:102-19. PubMed
  • Lank SM, Golbach BA, Creager HM, Wiseman RW, Keskin DB, Reinherz EL, Brusic V, O'Connor DH. Ultra-high resolution HLA genotyping and allele discovery by highly multiplexed cDNA amplicon pyrosequencing. BMC Genomics 2012; 13:378. PubMed
  • Riemer AB, Keskin DB, Reinherz EL. Identification and validation of reference genes for expression studies in human keratinocyte cell lines treated with and without interferon-粒 - a method for qRT-PCR reference gene determination. Exp Dermatol 2012; 21:625-9. PubMed
  • Reinherz EL. Pharmacology: A false sense of non-self. Nature 2012; 486:479-81. PubMed
  • Zhang Z, Tongchusak S, Mizukami Y, Kang YJ, Ioji T, Touma M, Reinhold B, Keskin DB, Reinherz EL, Sasada T. Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery. Biomaterials 2011; 32:3666-78. PubMed
  • Anderson KS, Zeng W, Sasada T, Choi J, Riemer AB, Su M, Drakoulakos D, Kang YJ, Brusic V, Wu C, Reinherz EL. Impaired tumor antigen processing by immunoproteasome-expressing CD40-activated B: cells and dendritic cells. Cancer Immunol Immunother 2011. PubMed
  • Zhang GL, Deluca DS, Keskin DB, Chitkushev L, Zlateva T, Lund O, Reinherz EL, Brusic V. MULTIPRED2: A computational system for large-scale identification of peptides predicted to bind to HLA supertypes and alleles. J Immunol Methods 2011. PubMed
  • Reinhold B, Keskin DB, Reinherz EL. Molecular Detection of Targeted Major Histocompatibility Complex I-Bound Peptides Using a Probabilistic Measure and Nanospray MS(3) on a Hybrid Quadrupole-Linear Ion Trap. Anal Chem 2010. PubMed
  • Riemer AB, Keskin DB, Zhang G, Handley M, Anderson KS, Brusic V, Reinhold B, Reinherz EL. A conserved E7-derived cytotoxic T lymphocyte epitope expressed on human papillomavirus 16-transformed HLA-A2+ epithelial cancers. J Biol Chem 2010; 285:29608-22. PubMed
  • Kim ST, Touma M, Takeuchi K, Sun ZY, Dave VP, Kappes DJ, Wagner G, Reinherz EL. Distinctive CD3 heterodimeric ectodomain topologies maximize antigen-triggered activation of alpha beta T cell receptors. J Immunol 2010; 185:2951-9. PubMed
  • Zhang W, Choi J, Zeng W, Rogers SA, Alyea EP, Rheinwald JG, Canning CM, Brusic V, Sasada T, Reinherz EL, Ritz J, Soiffer RJ, Wu CJ. Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion. Clin Cancer Res 2010; 16:2729-39. PubMed
  • Kim ST, Takeuchi K, Sun ZY, Touma M, Castro CE, Fahmy A, Lang MJ, Wagner G, Reinherz EL. The alphabeta T cell receptor is an anisotropic mechanosensor. J Biol Chem 2009; 284:31028-37. PubMed
  • Song L,Sun ZY,Coleman KE,Zwick MB,Gach JS,Wang JH,Reinherz EL,Wagner G,Kim M. Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface. Proc Natl Acad Sci U S A 2009; 106:9057-62. PubMed
  • Grandpre LE,Duke-Cohan JS,Ewald BA,Devoy C,Barouch DH,Letvin NL,Reinherz EL,Baden LR,Dolin R,Seaman MS. Immunogenicity of recombinant Modified Vaccinia Ankara following a single or multi-dose vaccine regimen in rhesus monkeys. Vaccine 2009; 27:1549-56. PubMed
  • Duke-Cohan JS,Wollenick K,Witten EA,Seaman MS,Baden LR,Dolin R,Reinherz EL. The heterogeneity of human antibody responses to vaccinia virus revealed through use of focused protein arrays. Vaccine 2009; 27:1154-65. PubMed
  • Waite AL, Schaner P, Richards N, Balci-Peynircioglu B, Masters SL, Brydges SD, Fox M, Hong A, Yilmaz E, Kastner DL, Reinherz EL, Gumucio DL. Pyrin Modulates the Intracellular Distribution of PSTPIP1. PLoS ONE 2009; 4:e6147. PubMed
  • Choi YI,Duke-Cohan JS,Ahmed WB,Handley MA,Mann F,Epstein JA,Clayton LK,Reinherz EL. PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla. Immunity 2008; 29:888-98. PubMed
  • Takeuchi K,Yang H,Ng E,Park SY,Sun ZY,Reinherz EL,Wagner G. Structural and functional evidence that Nck interaction with CD3epsilon regulates T-cell receptor activity. J Mol Biol 2008; 380:704-16. PubMed
  • Garcia-Boronat M,Diez-Rivero CM,Reinherz EL,Reche PA. PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery. Nucleic Acids Res 2008; 36:W35-41. PubMed
  • Wang JH, Mallis RJ, Reinherz EL. Immunodominant-peptide recognition: beta testing TCRalphabeta. Immunity 2008; 28:139-41. PubMed
  • Sun ZY, Oh KJ, Kim M, Yu J, Brusic V, Song L, Qiao Z, Wang JH, Wagner G, Reinherz EL. HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane. Immunity 2008; 28:52-63. PubMed
  • Lin HH,Zhang GL,Tongchusak S,Reinherz EL,Brusic V. Evaluation of MHC-II peptide binding prediction servers: applications for vaccine research. BMC Bioinformatics 2009; 9 Suppl 12:S22. PubMed
  • Lin HH, Ray S, Tongchusak S, Reinherz EL, Brusic V. Evaluation of MHC class I peptide binding prediction servers: applications for vaccine research. BMC Immunol 2008; 9:8. PubMed
  • Zhong W, Dixit SB, Mallis RJ, Arthanari H, Lugovskoy AA, Beveridge DL, Wagner G, Reinherz EL. CTL recognition of a protective immunodominant influenza A virus nucleoprotein epitope utilizes a highly restricted Vbeta but diverse Valpha repertoire: functional and structural implications. J Mol Biol 2007; 372:535-48. PubMed
  • Touma M, Antonini V, Kumar M, Osborn SL, Bobenchik AM, Keskin DB, Connolly JE, Grusby MJ, Reinherz EL, Clayton LK. Functional role for I kappa BNS in T cell cytokine regulation as revealed by targeted gene disruption. J Immunol 2007; 179:1681-92. PubMed
  • Aldaz-Carroll L, Xiao Y, Whitbeck JC, Ponce de Leon M, Lou H, Kim M, Yu J, Reinherz EL, Isaacs SN, Eisenberg RJ, Cohen GH. Major neutralizing sites on vaccinia virus glycoprotein B5 are exposed differently on variola virus ortholog B6. J Virol 2007; 81:8131-9. PubMed
  • Kim M, Qiao Z, Yu J, Montefiori D, Reinherz EL. Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state. Vaccine 2006; 25:5102-14. PubMed
  • Brusic V, Marina O, Wu CJ, Reinherz EL. Proteome informatics for cancer research: From molecules to clinic. Proteomics 2007; 7:976-991. PubMed
  • Touma M, Chang HC, Sasada T, Handley M, Clayton LK, Reinherz EL. The TCR C beta FG loop regulates alpha beta T cell development. J Immunol 2006; 176:6812-23. PubMed
  • Reche PA, Keskin DB, Hussey RE, Ancuta P, Gabduza D, Reinherz EL. Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes. Med Immunol 2006; 5:1. PubMed
  • Chang HC, Tan K, Ouyang J, Parisini E, Liu JH, Le Y, Wang X, Reinherz EL, Wang JH. Structural and mutational analyses of a CD8alphabeta heterodimer and comparison with the CD8alphaalpha homodimer. Immunity 2005; 23:661-71. PubMed
  • Attinger A, Devine L, Wang-Zhu Y, Martin D, Wang JH, Reinherz EL, Kronenberg M, Cheroutre H, Kavathas P. Molecular basis for the high affinity interaction between the thymic leukemia antigen and the CD8alphaalpha molecule. J Immunol 2005; 174:3501-7. PubMed
  • Sasada T, Touma M, Chang HC, Clayton LK, Wang JH, Reinherz EL. Involvement of the TCR Cbeta FG loop in thymic selection and T cell function. J Exp Med 2002; 195:1419-31. PubMed
  • Crawford K, Gabuzda D, Pantazopoulos V, Xu J, Clement C, Reinherz E, Alper CA. Circulating CD2+ monocytes are dendritic cells. J Immunol 1999; 163:5920-8. PubMed
  • Kern P, Hussey RE, Spoerl R, Reinherz EL, Chang HC. Expression, purification, and functional analysis of murine ectodomain fragments of CD8alphaalpha and CD8alphabeta dimers. J Biol Chem 1999; 274:27237-43. PubMed
  • Wang JH, Smolyar A, Tan K, Liu JH, Kim M, Sun ZY, Wagner G, Reinherz EL. Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors. Cell 1999; 97:791-803. PubMed
  • Wang J, Lim K, Smolyar A, Teng M, Liu J, Tse AG, Liu J, Hussey RE, Chishti Y, Thomson CT, Sweet RM, Nathenson SG, Chang HC, Sacchettini JC, Reinherz EL. Atomic structure of an alphabeta T cell receptor (TCR) heterodimer in complex with an anti-TCR fab fragment derived from a mitogenic antibody. EMBO J 1998; 17:10-26. PubMed
  • Liu J, Tse AG, Chang HC, Liu J, Wang J, Hussey RE, Chishti Y, Rheinhold B, Spoerl R, Nathenson SG, Sacchettini JC, Reinherz EL. Crystallization of a deglycosylated T cell receptor (TCR) complexed with an anti-TCR Fab fragment. J Biol Chem 1996; 271:33639-46. PubMed
  • Koyasu S, Hussey RE, Clayton LK, Lerner A, Pedersen R, Delany-Heiken P, Chau F, Reinherz EL. Targeted disruption within the CD3 zeta/eta/phi/Oct-1 locus in mouse. EMBO J 1994; 13:784-97. PubMed
  • Siliciano RF, Lawton T, Knall C, Karr RW, Berman P, Gregory T, Reinherz EL. Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion. Cell 1988; 54:561-75. PubMed
  • Richardson NE, Brown NR, Hussey RE, Vaid A, Matthews TJ, Bolognesi DP, Reinherz EL. Binding site for human immunodeficiency virus coat protein gp120 is located in the NH2-terminal region of T4 (CD4) and requires the intact variable-region-like domain. Proc Natl Acad Sci U S A 1988; 85:6102-6. PubMed
  • Hussey RE, Richardson NE, Kowalski M, Brown NR, Chang HC, Siliciano RF, Dorfman T, Walker B, Sodroski J, Reinherz EL. A soluble CD4 protein selectively inhibits HIV replication and syncytium formation. Nature 1988; 331:78-81. PubMed
  • Royer HD, Acuto O, Fabbi M, Tizard R, Ramachandran K, Smart JE, Reinherz EL. Genes encoding the Ti beta subunit of the antigen/MHC receptor undergo rearrangement during intrathymic ontogeny prior to surface T3-Ti expression. Cell 1984; 39:261-6. PubMed
  • Fabbi M, Acuto O, Smart JE, Reinherz EL. Homology of Ti alpha-subunit of a T-cell antigen-MHC receptor with immunoglobulin. Nature 1984; 312:269-71. PubMed
  • Weiss MJ, Daley JF, Hodgdon JC, Reinherz EL. Calcium dependency of antigen-specific (T3-Ti) and alternative (T11) pathways of human T-cell activation. Proc Natl Acad Sci U S A 1984; 81:6836-40. PubMed
  • Royer HD, Bensussan A, Acuto O, Reinherz EL. Functional isotypes are not encoded by the constant region genes of the beta subunit of the T cell receptor for antigen/major histocompatibility complex. J Exp Med 1984; 160:947-52. PubMed
  • Meuer SC, Hussey RE, Fabbi M, Fox D, Acuto O, Fitzgerald KA, Hodgdon JC, Protentis JP, Schlossman SF, Reinherz EL. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell 1984; 36:897-906. PubMed
  • Meuer SC, Cooper DA, Hodgdon JC, Hussey RE, Fitzgerald KA, Schlossman SF, Reinherz EL. Identification of the receptor for antigen and major histocompatibility complex on human inducer T lymphocytes. Science 1983; 222:1239-42. PubMed
  • Acuto O, Hussey RE, Fitzgerald KA, Protentis JP, Meuer SC, Schlossman SF, Reinherz EL. The human T cell receptor: appearance in ontogeny and biochemical relationship of alpha and beta subunits on IL-2 dependent clones and T cell tumors. Cell 1983; 34:717-26. PubMed
  • Meuer SC, Acuto O, Hussey RE, Hodgdon JC, Fitzgerald KA, Schlossman SF, Reinherz EL. Evidence for the T3-associated 90K heterodimer as the T-cell antigen receptor. Nature 1983; 303:808-10. PubMed
  • Meuer SC, Hussey RE, Hodgdon JC, Hercend T, Schlossman SF, Reinherz EL. Surface structures involved in target recognition by human cytotoxic T lymphocytes. Science 1982; 218:471-3. PubMed
  • Meuer SC, Schlossman SF, Reinherz EL. Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci U S A 1982; 79:4395-9. PubMed
  • Reinherz EL, Kung PC, Goldstein G, Levey RH, Schlossman SF. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A 1980; 77:1588-92. PubMed
  • Reinherz EL, Kung PC, Goldstein G, Schlossman SF. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A 1979; 76:4061-5. PubMed
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