Major Research Areas

Publications

Imaging of the NK cell: Target cell Immune Synapse

Vyas, Y.M., Maniar, H., Lyddane, C.E., Sadelain, M., and Dupont, B. Ligand binding to inhibitory killer cell Ig-like receptors induces co-localization with Src Homology Domain 2-containing Protein Tyrosine Phosphatase 1 and interruption of ongoing activation signals. J Immunol 2004; 173:1571-1578

Vyas, Y.M., Mania, H., and Dupont, B. Visualization of signaling pathways and cortical cytoskeleton in cytolytic and noncytolytic natural killer cell immune synapses. Immunological Reviews 2002; 189:161-178

Vyas, Y.M., Maniar, H. and Dupont, B. Cutting Edge: Differential segregation of the Src homology 2-containing protein tyrosine phosphatase-1 within the early NK cell immune synapse distinguishes noncytolytic from cytolytic interactions. J Immunol 2002; 168:3150-3154

Vyas YM, Mehta KM, Morgan M, Maniar H, Butros L, Jung S, Burkhardt JK, Dupont B. Spatial organization of signal transduction molecules in the natural killer cell immune synapse during MHC class I-regulated non-cytolytic and cytolytic interactions. J Immunol 2001; 167:4358-4367

NK cell Immunobiology

Huang W, Ochs HD, Dupont B, Vyas YM. The Wiskott - Aldrich syndrome protein regulates nuclear translocation of NFAT2 and NK-kB (RelA) independently of its role in F-actin polymerization and actin cytoskeletal rearrangement. J Immunol 2005; 174:2602-2611

Doubrovina ES, Doubrovin MM, Vider E, Sisson RB, O'Reilly RJ, Dupont B, Vyas YM. Evasion from NK cell immunity by MHC Class I chain-related molecules expressing colon adenocarcinoma. J Immunol 2003; 171:6891-6899

NK Receptors, HLA Class I Genes and Hematopoietic Stem cell Transplantation

Hsu KC, Keever-Taylor CA, Wilton A, Pinto C, Heller G, Arkun K, O'Reilly RJ, Horowitz MM, Dupont B.Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood. 2005;105:4878-4884.

Dupont, B. and Hsu, K.C. Inhibitory killer Ig-like receptor (KIR) genes and HLA class I ligands in hematopoietic stem cell transplantation. Current Opin in Immun 2004; 16:634-643

Hsu KC, Chida S, Geraghty DE, Dupont B. The killer cell immunoglobulin-like receptor (KIR) genomic region: gene-order, haplotypes and allelic polymorphism. Immunological Reviews 2002; 190:40-52

Hsu, K.C., Liu, X-R., Selvakumar, A., Mickelson, E., O'Reilly, R.J., and Dupont, B. Killer Ig-like receptor (KIR) haplotype analysis by gene content: Evidence for genomic diversity with a minimum of six basic framework haplotypes, each with multiple subsets. J Immunol 2002; 169:5118-5129

Steffens U, Vyas Y, Dupont B, Selvakumar A. Nucleotide and amino acid sequence alignment for human killer cell inhibitory receptors (KIR), 1998. Tissue Antigens 1998; 51:398-413

Steffens U, Vyas Y, Dupont B, Selvakumar A. Genomic organization and allelic polymorphism of the human killer cell inhibitory receptor gene KIR103. Tissue Antigens 1997; 49:564-573

Signal Transduction in NK cells and T Cells

Marti F, Krause A, Post NH, Lyddane C, Dupont B, Sadelain M, King PD. Negative-feedback regulation of CD28 costimulation by a novel MAP-kinase phosphatase, MKP6. J Immunol 2001; 166:197-206

Marti F, Xu CW, Selvakumar A, Brent R, Dupont B, King PD. LCK phosphorylated human killer cell inhibitory receptors recruit and activate phosphatidylinositol 3-kinase. Proc Natl Acad Sci (USA) 1998; 95:11810-11815

King PD, Sadra A, Teng JM, Bell GM, Dupont B. CD2-mediated activation of the Tec-family tyrosine kinase ITK is controlled by proline-rich stretch-4 of the CD2 cytoplasmic tail. Intl Immunol 1998; 10:1009-1016

August A, Sadra A, Dupont B, Hanafusa H. Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the Pleckstrin homology domain of inducible T cell kinase. Proc Natl Acad Sci (USA) 1997; 94:11227-11232

King PD, Sadra A, Teng JM, Xiao-Rong L, Han A, Selvakumar A, August A, Dupont B. Analysis of CD28 cytoplasmic tail tyrosine residues as regulators and substrates for the protein tyrosine kinases, EMT and LCK. J Immunol 1997; 158:589-590

King PD, Sadra A, Han A, Liu XR, Sunder-Plassmann R, Reinherz EL, Dupont B. CD2 signaling in T cells involves tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK. Intl Immunol 1996; 8:1707-1714

August A, Dupont B. Association between MAPK and the zeta chain of the TCR with the SH2,3 domain of p56lck: differential regulation by TCR crosslinking. J Biol Chem 1996; 271:10054-10059

Teng JM, Liu XR, Mills GB, Dupont B. CD28 mediated cytotoxicity by the human leukemic natural killer cell line, YT, involves tyrosine phosphorylation, activation of phosphatidylinositol-3-kinase and protein kinase C. J Immunol 1996; 165:3222-3232

August A, Gibson S, Kawakami Y, Kawakami T, Mills GB, Dupont B. CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line. Proc Natl Acad Sci (USA) 1994; 91:9347-9351

Immunobiology of Hematopoietic Stem cell Transplantation

Koehne G, Smith KM, Ferguson TL, Williams RY, Heller G, Pamer EG, Dupont B, O'Reilly RJ. Quantitation, selection, and functional characterization of Epstein-Barr virus-specific and alloreactive T cells detected by intracellular interferon-ã production and growth of cytotoxic precursors. Blood 2002; 99:1730-1740

Petersdorf EW, Kollman C, Hurley CK, Dupont B, Nademanee A, Begovich AB, Weisdorf D, McGlave P. Effect of HLA class II gene disparity on clinical outcome in unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia: the U.S. National Marrow Donor Program Experience. Blood 2001; 98:2922-2929

Small TN, Avigan D, Dupont B, Smith K, Black P, Heller G, Polyak T, O'Reilly RJ. Immune reconstitution following T-cell depleted bone marrow transplantation: Effect of age and posttransplant graft rejection prophylaxis. Biol Blood and Marrow Transplant 1997; 3:65-75

Dupont, B. Immunology of hematopoietic stem cell transplantation: a brief review of its history. Immunol Rev 1997; 157:5-12

HLA Restriction of Anti-Tumor Immunity

Atanackovic D, Altorki NK, Stockert E, Williamson B, Jungbluth AA, Ritter E, Santiago D, Ferrara CA, Matsuo M, Selvakumar A, Dupont B, Chen YT, Hoffman EW, Ritter G, Old LJ, Gnjatic S. Vaccine-induced CD4+ T cell responses to MAGE-3 protein in lung cancer patients. J Immun 2004; 172:3289-3296

Gnjatic S, Atanackovic D, Jager E, Matsuo M, Selvakumar A, Altorki NK, Maki RG, Dupont B, Ritter G, Chen YT, Knuth A, Old LJ. Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: correlation with antibody responses. Proc Natl Acad Sci (USA) 2003; 100:8862-8867

Gnjatic S, Nagata Y, Jager E, Stockert E, Shankara S, Roberts BL, Mazzara GP, Lee SY, Dunbar PR, Dupont B, Cerundolo V, Ritter G, Chen YT, Knuth A, Old LJ. Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele. Proc Natl Acad Sci (USA) 2000; 97:10917-10922

Jager E, Nagata Y, Gnjatic S, Wada H, Stockert E, Karbach J, Dunbar PR, Lee SY, Jungbluth A, Jager D, Arand M, Ritter G, Cerundolo V, Dupont B, Chen YT, Old LJ, Knuth A. Monitoring CD8 T cell responses to NY-ESO-1: Correlation of humoral and cellular immune responses. Proc Natl Acad Sci (USA) 2000; 97:4760-4765

Key Publications from the Dupont Laboratory: 1971 - 1996

Dupont B, Nielsen LS, Svejgaard A. Relative importance of Four and LA loci in determining mixed-lymphocyte reaction. Lancet. 1971; 2:1336-1340

Dupont B, Andersen V, Hansen GS, Svejgaard A. Abnormal mixed lymphocyte reactions in the family of a patient with severe combined immunodeficiency. Transplantation. 1972; 14:557-563.

Dupont B, Andersen V, Ernst P, Faber V, Good RA, Hansen GS, Henriksen K, Jensen K, Juhl F, Killmann SA, Koch C, Muller-Berat N, Park BH, Svejgaard A, Thomsen M, Wiik A. Immunologic reconstitution in severe combined immunodeficiency with HL-A-incompatible bone marrow graft: donor selection by mixed lymphocyte culture. Transplant Proc. 1973; 5:905-908.

Bone-marrow transplantation from an HL-A non-identical but mixed-lymphocyte-culture identical donor. Lancet. 1973; 1:1146-1150.

Jersild C, Fog T, Hansen GS, Thomsen M, Svejgaard A, Dupont B. Histocompatibility determinants in multiple sclerosis, with special reference to clinical course. Lancet. 1973; 2:1221-1225.

Day NK, L'Esperance R, Good RA, Michael AF, Hansen JA, Dupont B, Jersild C. Hereditary C2 deficiency: Genetic studies and association with the HL-A system. J Exp Med. 1975; 141:1464-1469.

Ochs HD, Rosenfeld SI, Thomas ED, Giblett ER, Alper CA, Dupont B, Schaller JG, Gilliland BC, Hansen JA, Wedgwood RJ. Linkage between the gene (or genes) controlling synthesis of the fourth component of complement and the major histocompatibility complex. N Engl J Med. 1977; 296:470-475.

O'Reilly RJ, Dupont B, Pahwa S, Grimes E, Smithwick EM, Pahwa R, Schwartz S, Hansen JA, Siegal FP, Sorell M, Svejgaard A, Jersild C, Thomsen M, Platz P, L'Esperance P, Good RA. Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor. N Engl J Med. 1977; 297:1311-1318.

Dupont B, Oberfield SE, Smithwick EM, Lee TD, Levine LS. Close genetic linkage between HLA and congenital adrenal hyperplasia (21-hydroxylase deficiency). Lancet. 1977; 2:1309-1312.

O'Neill GJ, Yang SY, Tegoli J, Berger R, Dupont B. Chido and Rodgers blood groups are distinct antigenic components of human complement C4. Nature. 1978; 273:668-670.

O'Neill GJ, Yang SY, Dupont B. Two HLA-linked loci controlling the fourth component of human complement. Proc Natl Acad Sci USA. 1978; 75:5165-5169.

Levine LS, Zachmann M, New MI, Prader A, Pollack MS, O'Neill GJ, Yang SY, Oberfield SE, Dupont B. Genetic mapping of the 21-hydroxylase-deficiency gene within the HLA linkage group. N Engl J Med. 1978; 299:911-915.

Pollack MS, Maurer D, Levine LS, New MI, Pang S, Duchon M, Owens RP, Merkatz IR, Nitowsky BM, Sachs G, Dupont B. Prenatal diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency) by HLA typing. Lancet. 1979; 1:1107-1108.

Pollack MS, Schafer IA, Barford D, Dupont B. Prenatal identification of paternity. HLA typing helpful after rape. JAMA. 1980; 244:1954-1956.

Pollack MS, Ochs HD, Dupont B. HLA typing of cultured amniotic cells for the prenatal diagnosis of complement C4 deficiency. Clin Genet. 1980; 18:197-200.

Pollack MS, Kapoor N, Sorell M, Kim SJ, Christiansen FT, Silver DM, Dupont B, O'Reilly RJ. DR-positive maternal engrafted T cells in a severe combined immunodeficiency patient without graft-versus-host disease. Transplantation. 1980; 30:331-334.

Dinsmore RE, Straus DJ, Pollack MS, Woodruff JM, Garrett TJ, Young CW, Clarkson BD, Dupont B. Fatal graft-versus-host disease following blood transfusion in Hodgkin's disease documented by HLA typing. Blood. 1980; 55:831-834.

Reisner Y, Kapoor N, Kirkpatrick D, Pollack MS, Dupont B, Good RA, O'Reilly RJ. Transplantation for acute leukaemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells. Lancet. 1981; 2:327-331.

Kornbluth J, Flomenberg N, Dupont B. Cell surface phenotype of a cloned line of human natural killer cells. J Immunol. 1982; 129:2831-2837.

Flomenberg N, Dupont B, O'Reilly RJ, Hayward A, Pollack MS. The use of T cell culture techniques to establish the presence of an intrauterine-derived maternal T cell graft in a patient with severe combined immunodeficiency (SCID). Transplantation. 1983; 36:733-735.

Kernan NA, Knowles RW, Burns MJ, Broxmeyer HE, Lu L, Lee HM, Kawahata RT, Scannon PJ, Dupont B. Specific inhibition of in vitro lymphocyte transformation by an anti-pan T cell (gp67) ricin A chain immunotoxin. J Immunol. 1984; 133:137-146.

White PC, New MI, Dupont B. Cloning and expression of cDNA encoding a bovine adrenal cytochrome P-450 specific for steroid 21-hydroxylation. Proc Natl Acad Sci USA. 1984; 81:1986-1990.

White PC, Chaplin DD, Weis JH, Dupont B, New MI, Seidman JG. Two steroid 21-hydroxylase genes are located in the murine S region. Nature. 1984; 312:465-467.

White PC, New MI, Dupont B. HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P-450 specific for steroid 21-hydroxylation. Proc Natl Acad Sci USA. 1984; 81:7505-7509.

White PC, Grossberger D, Onufer BJ, Chaplin DD, New MI, Dupont B, Strominger JL. Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man. Proc Natl Acad Sci USA. 1985; 82:1089-1093.

Kernan NA, Flomenberg N, Collins NH, O'Reilly RJ, Dupont B. Quantitation of T lymphocytes in human bone marrow by a limiting dilution assay. Transplantation. 1985; 40:317-322.

Werkmeister JW, New MI, Dupont B, White PC. Frequent deletion and duplication of the steroid 21-hydroxylase genes. Am J Hum Genet. 1986; 39:461-469.

White PC, New MI, Dupont B. Structure of human steroid 21-hydroxylase genes. Proc Natl Acad Sci USA. 1986; 83:5111-5115.

Kernan NA, Collins NH, Juliano L, Cartagena T, Dupont B, O'Reilly RJ. Clonable T lymphocytes in T cell-depleted bone marrow transplants correlate with development of graft-v-host disease. Blood. 1986; 68:770-773.

Yang SY, Chouaib S, Dupont B. A common pathway for T lymphocyte activation involving both the CD3-Ti complex and CD2 sheep erythrocyte receptor determinants. J Immunol. 1986; 137:1097-1100.

Kernan NA, Flomenberg N, Dupont B, O'Reilly RJ. Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. Transplantation. 1987; 43:842-847.

Kernan NA, Byers V, Scannon PJ, Mischak RP, Brochstein J, Flomenberg N, Dupont B, O'Reilly RJ. Treatment of steroid-resistant acute graft-vs-host disease by in vivo administration of an anti-T-cell ricin A chain immunotoxin. JAMA. 1988; 259:3154-3157.

Trapani JA, Klein JL, White PC, Dupont B. Molecular cloning of an inducible serine esterase gene from human cytotoxic lymphocytes. Proc Natl Acad Sci USA. 1988; 85:6924-6928.

White PC, Vitek A, Dupont B, New MI. Characterization of frequent deletions causing steroid 21-hydroxylase deficiency. Proc Natl Acad Sci USA. 1988; 85:4436-4440.

Trapani JA, Mizuno S, Kang SH, Yang SY, Dupont B. Molecular mapping of a new public HLA class I epitope shared by all HLA-B and HLA-C antigens and defined by a monoclonal antibody. Immunogenetics. 1989; 29:25-32.

Trapani JA, Kwon BS, Kozak CA, Chintamaneni C, Young JD, Dupont B. Genomic organization of the mouse pore-forming protein (perforin) gene and localization to chromosome 10. Similarities to and differences from C9. J Exp Med. 1990; 171:545-557.

Fleischhauer K, Kernan NA, O'Reilly RJ, Dupont B, Yang SY. Bone marrow-allograft rejection by T lymphocytes recognizing a single amino acid difference in HLA-B44. N Engl J Med. 1990; 323:1818-1822.

Koulova L, Clark EA, Shu G, Dupont B. The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells. J Exp Med. 1991; 173:759-762.

Young JW, Koulova L, Soergel SA, Clark EA, Steinman RM, Dupont B. The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro. J Clin Invest. 1992; 90:229-237.

August A, Dupont B. CD28 of T lymphocytes associates with phosphatidylinositol 3-kinase. Int Immunol. 1994; 6:769-774.

Gibson S, August A, Kawakami Y, Kawakami T, Dupont B, Mills GB. The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling: LCK is required for optimal activation of EMT. J Immunol. 1996; 156:2716-2722.

August A, Dupont B. Association between mitogen-activated protein kinase and the zeta chain of the T cell receptor (TcR) with the SH2,3 domain of p56lck. Differential regulation by TcR cross-linking. J Biol Chem. 1996; 271:10054-10059.

Selvakumar A, Steffens U, Dupont B. NK cell receptor gene of the KIR family with two IG domains but highest homology to KIR receptors with three IG domains. Tissue Antigens. 1996; 48:285-294.

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