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. The refore, influencing the activation of the T-cell response in order to modify immune responsiveness is an obvious therapeutic goal. We have u sed a mouse model of response to Fel d I, the major cat protein allerg en in humans, to explore the ability of peptides derived from Fel d I to inhibit T-cell-dependent immune responses to the peptides themselve s and to larger polypeptides. T cells from B6CBAF1 mice respond to the Fel d I peptide IPC-2 after challenge with IPC-2. However, subcutaneo us tolerization with IPC-2 prevents this response as measured by produ ction of interleukins 2 and 4 and interferon gamma. Fel d I immunizati on 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 antib ody production in Fel d I-primed animals when they are subsequently ch allenged with peptide in adjuvant. Most of the cat-allergic human T-ce ll 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 adminis tration 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 t o the entire recombinant Fel d I chain 1. The ability to tolerize T-ce ll responses with subcutaneous injections suggests a practical approac h to treating human diseases with peptides containing T-cell epitopes.