Bacterial heat shock proteins enhance class II MHC antigen processing and presentation of chaperoned peptides to CD4+ T cells.
APCs process heat shock protein (HSP):peptide complexes to present HSP-chaperoned peptides on class I MHC molecules, but the ability of HSPs to contribute chaperoned peptides for class II MHC (MHC-II) Ag processing and presentation is unclear. Our studies revealed that exogenous bacterial HSPs (Escherichia coli DnaK and Mycobacterium tuberculosis HSP70) delivered an extended OVA peptide for processing and MHC-II presentation, as detected by T hybridoma cells. Bacterial HSPs enhanced MHC-II presentation only if peptide was complexed to the HSP, suggesting that the key HSP function was enhanced delivery or processing of chaperoned peptide Ag rather than generalized enhancement of APC function. HSP-enhanced processing was intact in MyD88 knockout cells, which lack most TLR signaling, further suggesting the effect was not due to TLR-induced induction of accessory molecules. Bacterial HSPs enhanced uptake of peptide, which may contribute to increased MHC-II presentation. In addition, HSPs enhanced binding of peptide to MHC-II molecules at pH 5.0 (the pH of vacuolar compartments), but not at pH 7.4, indicating another mechanism for enhancement of MHC-II Ag processing. Bacterial HSPs are a potential source of microbial peptide Ags during phagocytic processing of bacteria during infection and could potentially be incorporated in vaccines to enhance presentation of peptides to CD4+ T cells.
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Aaron A R
AA
Tobian
David H
DH
Canaday
Clifford V
CV
Harding
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000502:physiology; D001426:Bacterial Proteins / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology; D051193:Toll-Like Receptors
D015703:Antigens, CD; D001426:Bacterial Proteins; D018840:HSP70 Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D010047:Ovalbumin