Major T cell epitope-containing peptides can elicit strong antibody responses.
Peptides containing major T cell epitopes have the capacity to induce T cell anergy and have therefore been proposed for the treatment of allergic and autoimmune diseases. Such peptides should not be immunogenic, i. e. should not contain a B cell recognition site. We have evaluated in BALB/c mice the therapeutic potential of a 15-mer peptide (p21 - 35) derived from Der p2, a major allergen of the house dust mite Dermatophagoides pteronyssinus, which contains a dominant T cell epitope but is not recognized by antibodies to Der p2. Unexpectedly, p21 - 35 elicited strong immune responses, suggesting the presence of a cryptic B cell epitope. Similar results were obtained with mice of three additional MHC haplotypes. A core sequence of four amino acids (Ile-Ile-His-Arg) corresponding to residues 28 - 31 was shared by the B and T cell epitopes. Critical residues for B cell recognition were Arg31 and Lys33, while Ile28 was essential for T cell recognition. A Lys33Ala mutant of p21 - 35 still activated T cells but had much reduced immunogenic properties, making it a suitable alternative peptide for T cell anergy induction. Careful investigation of the immunogenic potential of peptides used to induce T cell anergy should be carried out prior to their clinical application.
Wu
B
B
Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
Toussaint
G
G
Vander Elst
L
L
Granier
C
C
Jacquemin
M G
MG
Saint-Remy
J M
JM
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D039741:Antigens, Dermatophagoides; D001402:B-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006239:Haplotypes; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*
D000485:Allergens; D039741:Antigens, Dermatophagoides; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D010446:Peptide Fragments