An immunodominant epitope from mycobacterial 65-kDa heat shock protein protects against pristane-induced arthritis.
Previous studies showed that mice with pristane-induced arthritis (PIA) and those protected from the disease by preimmunization with mycobacterial 65-kDa heat shock protein (hsp65) possess raised immune responses to hsp65. Additionally, T cells from hsp65-protected mice, but not from pristane-injected or normal mice, produced the Th2-associated cytokines IL-4, IL-5, and IL-10 in response to stimulation with hsp65. Here we demonstrate that the specificity of the immune response to hsp65 and related heat shock protein (hsps) differs between protected and PIA mice. T cells from hsp65-protected mice respond to the bacterial hsps tested but not to the mammalian homologue, hsp58. Similarly, they exhibit high serum titers of anti-hsp65 Abs, yet they have virtually undetectable levels of anti-hsp58 IgG. By contrast, both cellular and humoral immune responses are detectable to bacterial and mammalian hsps in mice with PIA. An immunodominant T cell epitope has been identified in hsp65-protected mice corresponding to amino acids 261-271 from hsp65. Immunization of mice, either before or after the induction of arthritis, with this bacterial peptide, but not its mammalian homologue, protects mice from the development of PIA, and protection is associated with the production of Th2-type cytokines. Other experiments revealed that T cells primed with bacterial 261-271 or the mammalian homologue do not cross-react at the proliferative or cytokine level. These results demonstrate that an hsp65 peptide-specific Th2 response confers protection from PIA but do not support the idea that protection is mediated by a cross-reaction with self hsp58 in the joints.
Thompson
S J
SJ
Department of Pathology and Microbiology, University of Bristol, UK. steve.j.thompson@bris.ac.uk
Francis
J N
JN
Siew
L K
LK
Webb
G R
GR
Jenner
P J
PJ
Colston
M J
MJ
Elson
C J
CJ
D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000008:administration & dosage / Q000276:immunology*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000008:administration & dosage* / Q000276:immunology; D007166:Immunosuppressive Agents; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013729:Terpenes
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016056:Immunodominant Epitopes; D007166:Immunosuppressive Agents; D013729:Terpenes; C074119:heat-shock protein 65, Mycobacterium; C009042:pristane; D018833:Chaperonins