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Research
Interests |
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Our research interests are focused on the mechanisms of cross-priming of antigens during immune responses to cancer, viruses and autoimmunity. The pursuit of this area stems from the observations that in a good number of situations Heat Shock Proteins (HSPs) are both necessary and sufficient for cross-presentation. HSPs are adept at this because of several unique properties:
(i) HSPs chaperone peptides
(ii) They bind to HSP-receptors (CD91) for endocytosis
(iii)They can stimulate immune cells to up-regulate costimulation
HSPs thus elicit remarkable immune responses specific for the peptides they chaperone. The laboratory is using these observations to examine new facets of antigen presentation and also to develop novel ways of immunotherapy of cancer, infectious disease and autoimmune disorders. A related area of research examines how other ligands for the HSP-receptorCD91 interact with the immune system. In the past few years we have shown that a2-macroglobulin, a CD91 ligand, though not a bonafide HSP, shares the immunogenic properties of HSPs and can elicit immune responses specific to (peptide) substrates that it chaperones. We are currently exploring the identification of naturally formed a2M-substrate complexes and the potential of these immunogenic complexes to be used as therapeutic agents in cancer and infectious disease.
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Selected
Publications |
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- Binder RJ, Srivastava PK. Peptides chaperoned by heat-shock proteins are a necessary and sufficient source of antigen in the cross-priming of CD8+ T cells. Nat Immunol 6:593-599. 2005.
- SenGupta D, Norris PJ, Suscovich TJ, Hassan-Zahraee M, Moffett HF, Trocha A, Draenert R, Goulder PJ, Binder RJ, Levey DL, Walker BD, Srivastava PK, Brander C. Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II. J Immunol 173:1987-1993. 2004.
- Binder RJ, Srivastava PK. Essential role of CD91 in re-presentation of gp96-chaperoned peptides. Proc Natl Acad Sci U S A. 101:6129-6133. 2004.
- Stebbing J, Gazzard B, Portsmouth S, Gotch F, Kim L, Bower M, Mandalia S, Binder R, Srivastava P, Patterson S. Disease associated dendritic cells respond to disease-specific antigens through the common heat shock protein receptor. Blood 102:1806-1814. 2003.
- Binder RJ, Kumar SK, Srivastava PK. Naturally formed or artificially reconstituted non-covalent alpha2-macroglobulin-peptide complexes elicit CD91-dependent cellular immunity. Cancer Immunity 2:16. 2002.
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Other
Links |
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University of Pittsburgh |
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Office:
E1051 BSTWR |
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Lab:
W1006 BSTWR |
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Phone:
412.383.7722 |
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Fax:412.383.8096 |
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rjb42@pitt.edu |
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Academic
Affiliations |
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- Assistant Professor, Department of Immunology, University of Pittsburgh School of Medicine
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Education |
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- B.S. - University of Ghana
- Ph.D. - University of Connecticut
- Postdoc - University of Connecticut
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Grant
Support |
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Lab
Personnel |
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Research Associate
Laura Kropp |
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