Resistance to adjuvant arthritis is due to protective antibodies against heat shock protein surface epitopes and the induction of IL-10 secretion.
Adjuvant arthritis (AA) is an experimental model of autoimmune arthritis that can be induced in susceptible strains of rats such as inbred Lewis upon immunization with CFA. AA cannot be induced in resistant strains like Brown-Norway or in Lewis rats after recovery from arthritis. We have previously shown that resistance to AA is due to the presence of natural as well as acquired anti-heat shock protein (HSP) Abs. In this work we have studied the fine specificity of the protective anti-HSP Abs by analysis of their interaction with a panel of overlapping peptides covering the whole HSP molecule. We found that arthritis-susceptible rats lack Abs to a small number of defined epitopes of the mycobacterial HSP65. These Abs are found naturally in resistant strains and are acquired by Lewis rats after recovery from the disease. Active vaccination of Lewis rats with the protective epitopes as well as passive vaccination with these Abs induced suppression of arthritis. Incubation of murine and human mononuclear cells with the protective Abs induced secretion of IL-10. Analysis of the primary and tertiary structure of the whole Mycobacterium tuberculosis HSP65 molecule indicated that the protective epitopes are B cell epitopes with nonconserved amino acid sequences found on the outer surface of the molecule. We conclude that HSP, the Ag that contains the pathogenic T cell epitopes in AA, also contains protective B cell epitopes exposed on its surface, and that natural and acquired resistance to AA is associated with the ability to respond to these epitopes.
Ulmansky
Rina
R
Clinical Immunology and Allergy Unit, Hadassah University Hospital, Jerusalem, Israel.
Cohen
Cyril J
CJ
Szafer
Fanny
F
Moallem
Eli
E
Fridlender
Zvi G
ZG
Kashi
Yechezkel
Y
Naparstek
Yaakov
Y
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000378:metabolism; D000954:Antigens, Surface / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins; D001666:Binding Sites, Antibody; D018834:Chaperonin 60 / Q000276:immunology / Q000378:metabolism; D018833:Chaperonins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007136:Immunoglobulins / Q000378:metabolism; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D017433:Protein Structure, Secondary; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index
D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D001500:BCG Vaccine; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D006360:Heat-Shock Proteins; D007136:Immunoglobulins; D010446:Peptide Fragments; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D018833:Chaperonins