Mycobacterium tuberculosis heat shock fusion protein enhances class I MHC cross-processing and -presentation by B lymphocytes.
Exogenous heat shock protein (HSP):peptide complexes are processed for cross-presentation of HSP-chaperoned peptides on class I MHC (MHC-I) molecules. Fusion proteins containing HSP and Ag sequences facilitate MHC-I cross-presentation of linked antigenic epitopes. Processing of HSP-associated Ag has been attributed to dendritic cells and macrophages. We now provide the first evidence to show processing of HSP-associated Ag for MHC-I cross-presentation by B lymphocytes. Fusion of OVA sequence (rOVA, containing OVA(230-359) sequence) to Mycobacterium tuberculosis HSP70 greatly enhanced rOVA processing and MHC-I cross-presentation of OVA(257-264):K(b) complexes by B cells. Enhanced processing was dependent on linkage of rOVA sequence to HSP70. M. tuberculosis HSP70-OVA fusion protein enhanced cross-processing by a CD91-dependent process that was independent of TLR4 and MyD88. The enhancement occurred through a post-Golgi, proteasome-independent mechanism. These results indicate that HSPs enhance delivery and cross-processing of HSP-linked Ag by B cells, which could provide a novel contribution to the generation of CD8(+) T cell responses. HSP fusion proteins have potential advantages for use in vaccines to enhance priming of CD8(+) T cell responses.
Tobian
Aaron A R
AA
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Harding
Clifford V
CV
Canaday
David H
DH
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D001426:Bacterial Proteins; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014617:Vacuoles / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; D015395:Histocompatibility Antigens Class I; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin