DOWN-REGULATION OF CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES ON ANTIGEN-PRESENTING CELLS AFTER INTERACTION WITH HELPER T-CELLS

The recognition of antigenic peptides by CD4(+) helper T cells is demo nstrated here to result in a dramatic (up to 90%) decrease in expressi on of major histocompatibility complex (MHC) class II molecules on the surface of antigen-presenting cells (APC). The reduction is selective to the class II isotype presenting the antigen, but if affects both a llelic forms of the same isotype in heterozygous APC. The observed MHC down-regulation requires a specific T cell receptor-peptide-class II interaction, a direct contact between T cell and APC, and the involvem ent of CD2 molecules. These findings have important implications for t he regulation of immune response, self tolerance, and autoimmunity.