B cell responses to paramyosin. Isotypic analysis and epitope mapping of filarial paramyosin in patients with onchocerciasis.
To examine the fine specificity of the human immune response to filarial paramyosin, the antigenicity of an expressed rcDNA (2.55 kb) of Dirofilaria immitis paramyosin was detailed by ELISA. Using sera from patients infected with Onchocerca volvulus, we analyzed both the entire paramyosin molecule and six subcloned fragments for their IgG, IgG subclasses, and IgE responses. Patients from both Guatemala (64% positive) and Ghana (100% positive) reacted to paramyosin with specific IgG levels above normal controls. Although there was no anti-paramyosin subclass restriction common to all patients, the IgG3 response in the Ghananians was significantly greater than that of Guatemalans (p less than 0.001). IgE anti-paramyosin responses showed positive correlations with IgG2 (p less than 0.001), IgG4 (p less than 0.002), and IgG1 (p less than 0.04) responses. Epitope mapping using the IgG response to the six subclones demonstrated preferential recognition of the amino terminal end of the molecule (nucleotides 1 to 360). IgG2 reactivity was clearly localized to the most amino-terminal 120 amino acids, and the IgG4 antibodies recognized amino acids immediately adjacent to this fragment. These studies examining the fine specificity of anti-filarial immune reactions should provide a method for understanding how parasites either evade or induce host immune responses.
Steel
C
C
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Limberger
R J
RJ
McReynolds
L A
LA
Ottesen
E A
EA
Nutman
T B
TB
D000293:Adolescent; D000328:Adult; D000818:Animals; D000909:Antibodies, Helminth / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology*; D004183:Dirofilaria immitis / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis / Q000145:classification; D007132:Immunoglobulin Isotypes / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009855:Onchocerciasis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D014335:Tropomyosin / Q000276:immunology*
D000909:Antibodies, Helminth; D000939:Epitopes; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D010446:Peptide Fragments; D014335:Tropomyosin; D007073:Immunoglobulin E