Antigen processing by macrophages: definition of the ligand recognized by T-inducer cells

An interaction between antigen and macrophage-like cells which display I region gene products [antigen-presenting cells (APC)] is necessary for activation of inducer T cell clones. The specificity of inducer cell activation has been found to be major histocompatibility complex (MHC)-restricted and antigen specific. This is thought to reflect formation of a ligand consisting of MHC class II gene products associated in some way with foreign protein. A panel of inducer T cell clones with different activation specificities and homogeneous lines of APC expressing different MHC haplotypes was used to define this ligand. We isolated a product formed after interaction between antigen and APC expressing defined MHC products. This ligand binds only to the T cell clones that are specifically activated by the same antigen and APC as judged by tritiated thymidine incorporation. The ligand is composed of two moieties: I-A determinants and the foreign protein ("antigen"). Coelution and sequential precipitation studies of the two moieties indicate that the nominal antigen and MHC product are tightly linked. The implications of these findings are discussed.