Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d I.
T cells control the majority of antigen-specific immune responses. Therefore, influencing the activation of the T-cell response in order to modify immune responsiveness is an obvious therapeutic goal. We have used a mouse model of response to Fel d I, the major cat protein allergen in humans, to explore the ability of peptides derived from Fel d I to inhibit T-cell-dependent immune responses to the peptides themselves and to larger polypeptides. T cells from B6CBAF1 mice respond to the Fel d I peptide IPC-2 after challenge with IPC-2. However, subcutaneous tolerization with IPC-2 prevents this response as measured by production of interleukins 2 and 4 and interferon gamma. Fel d I immunization of B6D2F1 mice results in T-cell responses primarily to one peptide derived from Fel d I. Injecting this peptide in soluble form inhibits T-cell activation (as measured by interleukin 2 production) and antibody production in Fel d I-primed animals when they are subsequently challenged with peptide in adjuvant. Most of the cat-allergic human T-cell response to Fel d I is specific for two peptides on one of its two chains. Immunization of B6CBAF1 mice with recombinant Fel d I chain 1 results in T-cell responses to the same peptides. Subcutaneous administration of these two peptides, which contain some, but not all, of the T-cell epitopes from Fel d I chain I, decreases the T-cell response to the entire recombinant Fel d I chain 1. The ability to tolerize T-cell responses with subcutaneous injections suggests a practical approach to treating human diseases with peptides containing T-cell epitopes.
Briner
T J
TJ
ImmuLogic Pharmaceutical Corp., Waltham, MA 02154.
Kuo
M C
MC
Keating
K M
KM
Rogers
B L
BL
Greenstein
J L
JL
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D002415:Cats; D002460:Cell Line; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000485:Allergens; D006023:Glycoproteins; D007074:Immunoglobulin G; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; C059296:Fel d 1 protein, Felis domesticus