Antigenic peptides complexed to phylogenically diverse Hsp70s induce differential immune responses.
The Hsp70 class of heat shock proteins (Hsps) has been implicated at multiple points in the immune response, including initiation of proinflammatory cytokine production, antigen recognition and processing, and phenotypic maturation of antigen-presenting cells (APCs). This class of chaperones is highly conserved in both sequence and structure, from prokaryotes to higher eukaryotes. In all cases, these chaperones function to bind short segments of either peptides or proteins through an adenosine triphosphate-dependent process. In addition to a possible role in antigen presentation, these chaperones have also been proposed to function as a potent adjuvant. We compared 4 evolutionary diverse Hsp70s, E. coli DnaK, wheat cytosolic Hsc70, plant chloroplastic CCS1, and human Hsp70, for their ability to prime and augment a primary immune response against herpes simplex virus-1 (HSV1). We discovered that all 4 Hsp70s were highly effective as adjuvants displaying similar ability to lipopolysaccharides in upregulating cytokine gene expression. In addition, they were all capable of inducing phenotypic maturation of APCs, as measured by the display of various costimulatory molecules. However, only the human Hsp70 was able to mediate sufficient cross-priming activity to afford a protective immune response to HSV1, as judged by protection from a lethal viral challenge, in vitro proliferation, cytotoxicity, and intracellular interferon-gamma production. The difference in immune response generated by the various Hsp70s could possibly be due to their differential ability to interact productively with other coreceptors and different regulatory cochaperones.
Kumaraguru
Udayasankar
U
Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA. udayk@utk.edu
Gouffon
C A
CA
Ivey
R A
RA
Rouse
Barry T
BT
Bruce
Barry D
BD
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D010455:Peptides / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides