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17 results on '"Bunker, Jeffrey J."'

6. Specificity of Homeostatic IgA

Author

Bunker, Jeffrey J

Subjects
FOS: Clinical medicine, FOS: Biological sciences, Immunology, Microbiology
Abstract

A large fraction of the intestinal commensal microbiota is coated with IgA antibodies during homeostatic conditions, but the strategy and the mechanisms deployed to confront this immense diversity of bacterial antigens have remained elusive. Converging studies indicate that homeostatic IgA responses employ a highly polyreactive repertoire to bind broad but distinct subsets of microbiota. These antibody responses develop in the presence of limited T cell help, with low rates of somatic mutations and little affinity maturation. This new perspective contrasts with the classical paradigm of T cell-dependent, high-affinity antibody responses elicited by mucosal pathobionts, pathogens, and vaccines, and provides a simple immunological solution to the challenge of microbiota antigenic complexity. It also raises several fundamental issues, including how polyreactive specificities are generated and selected in the IgA repertoire, how these antibodies exert their effector functions, and how they coexist or overlap with other immune responses during homeostasis and disease.

Published
2018
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13. A negative feedback loop mediated by the Bcl6–cullin 3 complex limits Tfh cell differentiation

Author

Mathew, Rebecca, primary, Mao, Ai-ping, additional, Chiang, Andrew H., additional, Bertozzi-Villa, Clara, additional, Bunker, Jeffrey J., additional, Scanlon, Seth T., additional, McDonald, Benjamin D., additional, Constantinides, Michael G., additional, Hollister, Kristin, additional, Singer, Jeffrey D., additional, Dent, Alexander L., additional, Dinner, Aaron R., additional, and Bendelac, Albert, additional

Published
2014
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14. Elevated T Cell Receptor Signaling Identifies a Thymic Precursor to the TCRαβ+CD4-CD8β- Intraepithelial Lymphocyte Lineage.

Author

McDonald, Benjamin D., Bunker, Jeffrey J., Ishizuka, Isabel E., Jabri, Bana, and Bendelac, Albert

Subjects
*T cell receptors, *CELLULAR signal transduction, *CD4 antigen, *LYMPHOCYTES, *EPITHELIAL cells, *GENE expression
Abstract

The developmental pathway of intestinal TCRαβ+CD4- CD8β- intraepithelial lymphocytes (unconventional iIELs) has remained elusive. Bendelac and colleagues demonstrate that expression of unconventional iIEL TCRs in thymocytes causes negative selection and that unconventional iIELs are derived from rare escapees of cortical negative selection. [ABSTRACT FROM AUTHOR]

Published
2014
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15. Specificity of Homeostatic IgA

Author

Bunker, Jeffrey J

Abstract

A large fraction of the intestinal commensal microbiota is coated with IgA antibodies during homeostatic conditions, but the strategy and the mechanisms deployed to confront this immense diversity of bacterial antigens have remained elusive. Converging studies indicate that homeostatic IgA responses employ a highly polyreactive repertoire to bind broad but distinct subsets of microbiota. These antibody responses develop in the presence of limited T cell help, with low rates of somatic mutations and little affinity maturation. This new perspective contrasts with the classical paradigm of T cell-dependent, high-affinity antibody responses elicited by mucosal pathobionts, pathogens, and vaccines, and provides a simple immunological solution to the challenge of microbiota antigenic complexity. It also raises several fundamental issues, including how polyreactive specificities are generated and selected in the IgA repertoire, how these antibodies exert their effector functions, and how they coexist or overlap with other immune responses during homeostasis and disease.

Published
2019

16. N 5-Phosphonoacetyl-l-ornithine (PALO): A convenient synthesis and investigation of influence on regulation of amino acid biosynthetic genes in Saccharomyces cerevisiae

Author

Johnson, Brad, Steadman, Rachel, Patefield, Krista D., Bunker, Jeffrey J., Atkin, Audrey L., and Dussault, Patrick

Subjects
*SACCHAROMYCES cerevisiae, *AMINO acid synthesis, *GENETIC regulation, *BIOSYNTHESIS, *ARGININE, *ORNITHINE carbamoyltransferase, *ENZYME inhibitors, *GENE expression
Abstract

Abstract: A scalable four-step synthesis of the ornithine transcarbamylase inhibitor N 5-phosphonoacetyl-l-ornithine (PALO) is achieved through boroxazolidinone protection of ornithine. Investigations in the model organism Saccharomyces cerevisiae found that, in contrast to a previous report, PALO did not influence growth rate or expression of genes involved in arginine metabolism. [Copyright &y& Elsevier]

Published
2011
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17. Elevated T cell receptor signaling identifies a thymic precursor to the TCRαβ(+)CD4(-)CD8β(-) intraepithelial lymphocyte lineage.

Author

McDonald BD, Bunker JJ, Ishizuka IE, Jabri B, and Bendelac A

Subjects
Animals, Antigens, CD biosynthesis, Antigens, CD genetics, Antigens, CD immunology, Antigens, Differentiation, T-Lymphocyte biosynthesis, Antigens, Differentiation, T-Lymphocyte genetics, Antigens, Differentiation, T-Lymphocyte immunology, Apoptosis immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Cell Lineage immunology, Cells, Cultured, Clonal Deletion immunology, Histocompatibility Antigens Class I immunology, Histocompatibility Antigens Class II immunology, Lectins, C-Type biosynthesis, Lectins, C-Type genetics, Lectins, C-Type immunology, Mice, Mice, Transgenic, Programmed Cell Death 1 Receptor biosynthesis, Programmed Cell Death 1 Receptor genetics, Programmed Cell Death 1 Receptor immunology, Signal Transduction immunology, CD4-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes cytology, Cell Differentiation immunology, Receptors, Antigen, T-Cell, alpha-beta immunology
Abstract

The origin and developmental pathway of intestinal T cell receptor αβ(+) CD4(-)CD8β(-) intraepithelial lymphocytes (unconventional iIELs), a major population of innate-like resident cytolytic T cells, have remained elusive. By cloning and expressing several TCRs isolated from unconventional iIELs, we identified immature CD4(lo)CD8(lo)(DP(lo))CD69(hi)PD-1(hi) thymocytes as the earliest postsignaling precursors for these cells. Although these precursors displayed multiple signs of elevated TCR signaling, a sizeable fraction of them escaped deletion to selectively engage in unconventional iIEL differentiation. Conversely, TCRs cloned from DP(lo)CD69(hi)PD-1(hi) thymocytes, a population enriched in autoreactive thymocytes, selectively gave rise to unconventional iIELs upon transgenic expression. Thus, the unconventional iIEL precursor overlaps with the DP(lo) population undergoing negative selection, indicating that, concomitant with the downregulation of both CD4 and CD8 coreceptors, a balance between apoptosis and survival signals results in outcomes as divergent as clonal deletion and differentiation to the unconventional iIEL lineage., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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