SELECTIVE IMMUNOSUPPRESSION BY ADMINISTRATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-BINDING PEPTIDES .2. PREVENTIVE INHIBITION OF PRIMARY AND SECONDARY INVIVO ANTIBODY-RESPONSES

The self-mouse lysozyme peptide corresponding to residues 46-62 (ML46- 62) binds to the major histocompatibility complex (MHC) class II molec ules I-A(k) and it selectively inhibits, when coinjected with antigen, priming of I-A(k)-restricted, antigen-specific T cells. We demonstrat e that administration of ML46-62 also inhibits in vivo antibody respon ses induced by I-A(k)-restricted T helper cells. ML46-62 is able to pr event the primary anti-hen egg white lysozyme (HEL) antibody response induced by the entire HEL molecule in B10.A(4R) mice, expressing only I-A(k) molecules, but not in mice of H-2d haplotype. ML46-62 also stro ngly decreases, in B10.A(4R) mice, the antibody response to ribonuclea se A, a protein antigen unrelated to the MHC blocker, indicating that MHC blockade is the mechanism leading to inhibition of antibody respon se. This is further supported by the concomitant decrease, in vivo, of complex formation between immunodominant HEL peptides and I-A(k) mole cules, preventing I-A(k)-restricted T cell induction. Administration o f ML46-62 after antigen priming does not affect ongoing antibody respo nses, as expected from MHC blockade. A single injection of ML46-62 at the time of protein antigen priming precludes not only the primary, bu t also the secondary antibody response to a subsequent challenge with soluble protein, even when the challenge is performed several months a fter priming. Coinjection of antigen and MHC antagonist inhibits produ ction of all antibody isotypes equally well, suggesting that MHC class II blockade affects both Th1- and Th2-type T helper cells. Therefore, these results indicate that administration of MHC class II-binding pe ptides can efficiently and selectively prevent the induction of T cell -dependent primary and secondary in vivo antibody responses by blockin g antigen presentation to class II-restricted T helper cells.