TH1 CLONES THAT SUPPRESS IGG2A(B) SPECIFICALLY RECOGNIZE AN ALLOPEPTIDE DETERMINANT COMPRISING RESIDUES 435-451 OF GAMMA-2A(B)

We have previously reported that gamma2a(b)/I-A(d)-Specific Th1 clones from BALB/c mice (gamma2a(a), H-2d) mediated a long-lasting, selective suppression of serum IgG2a(b) levels when transferred to newborn (BALB/c x B10.D2)F1 (gamma2a/b H-2d) mice (Bartnes, K. and Hannestad, K. Eur. J. Immunol. 1991. 21: 2365). We here analyze the peptide specificity of hybridomas derived from two suppressive T cell clones. The shortest synthetic peptide with optimal antigenicity comprises gamma2a(b) residues 435-451 (Kabat numbering). The determinant core encompasses the gamma2a(b) 440-446 (KLRVQKS) sequence which contains an I-A(d) allele-specific motif. Challenge with single amino acid-substituted gamma2a(b) 435-447 analogs revealed that residues K440, R442 and K445 which are shared by the autologous and allogeneic gamma2a, as well as residues Q444 and S446 which represent allogeneic differences, are critical for recognition.We obtained evidence thal K440, R442 and Q444 are epitope residues, while K445 and S446 contribute to anchoring of the peptide to I-A(d). Amino acids located outside of the core also influence antigenicity, the most striking effect being a 340-870-fold augmentation of potency when gamma2a(b) 437-451 is extended by F436. IgG2a(b) required processing in order to stimulate the hybridomas.The data support the contention that the Th1 clones specific for Fc of gamma2a(b) mediated IgG2a(b) suppression by cognate interaction with sIgG2a(b+) B cells that presented a Cgamma2a(b) peptide(s) derived from their endogenous Ig on major histocompatibility complex class II. The T cells cross-reacted weakly with peptide 435-451 of the autologous gamma2a(a) allotype. This opens the possibility that self-peptides from Ig C regions can target B cells for regulatory interactions with autologous Th cells.