The adjuvant effects of Mycobacterium tuberculosis heat shock protein 70 result from the rapid and prolonged activation of antigen-specific CD8+ T cells in vivo.
Heat shock protein 70 (hsp70) is a potent adjuvant that links innate and adaptive immune responses. To study how hsp70 activates naive CD8(+) T cells in vivo, we tracked Ag-specific CD8(+) T cells in mice immunized with a fusion protein containing chicken OVA linked to hsp70 derived from Mycobacterium tuberculosis (OVA.TBhsp70). On a molar basis, OVA.TBhsp70 was several hundred times more effective than OVA peptide plus CFA in eliciting specific CD8(+) T cell responses. Immunization with OVA.TBhsp70 activated >90% of detectable OVA-specific CD8(+) T cells within 3 days and led to the persistence of cytotoxic effectors for at least 17 days. These studies demonstrate that the potent adjuvant effect of M. tuberculosis hsp70 results from the relatively complete, rapid, and durable activation of Ag-specific CD8(+) T cells.
Harmala
Lisa A E
LA
Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Ingulli
Elizabeth G
EG
Curtsinger
Julie M
JM
Lucido
Michelle M
MM
Schmidt
Clint S
CS
Weigel
Brenda J
BJ
Blazar
Bruce R
BR
Mescher
Matthew F
MF
Pennell
Christopher A
CA
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001426:Bacterial Proteins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line / Q000637:transplantation; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004527:Egg Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005620:Freund's Adjuvant / Q000008:administration & dosage; D005822:Genetic Vectors / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000032:analysis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000943:Antigens, Differentiation; D001426:Bacterial Proteins; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; D008070:Lipopolysaccharides; C110366:OVA-8; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin; D005620:Freund's Adjuvant