MODIFICATION OF HUMAN T-CELL RESPONSES BY ALTERED PEPTIDE LIGANDS - ANEW APPROACH TO ANTIGEN-SPECIFIC MODIFICATION

Human CD4+ T-cells recognize antigenic peptides in the context of huma n leukocyte antigen (HLA) class II molecules and produce various lymph okines to proliferate and activate other cells, It was once considered that the T-cell response is an all or nothing type event, but recent studies have clearly indicated that T-cells show many different types of activation in recognition of altered ligands for T-cell receptors ( TCR), In this review, we summarize our recent findings on the human CD 4+ T-cell response to altered peptide ligands (APL); peptides carrying single residue substitutions in antigenic peptides, We observed the f ollowing: 1) TCR antagonism for T-cell clones reactive to non-self or autoantigenic peptides, 2) partial activation (agonism) without cell p roliferation, including production of lymphokines and increases in cel l size, and in expression levels of several cell surface proteins or s urvival time in the absence of antigenic stimulus, 3) augmentation in cell proliferation and production of interferon-gamma (IFN-gamma) and granulocyte monocyte colony stimulating factor (GM-CSF), 4) augmentati on of interleukin (IL)-12 production by antigen presenting cell (APC) and the subsequent augmented production of IFN-gamma by T-cells, This information provides basic knowledge regarding the characteristics of T-cell recognition of antigens and the subsequent activation, and a no vel method for modification of human T-cell responses by altered pepti de ligands (APLs), as a possible candidate for antigen-specific immuno potentiating or immunosuppressive therapy against autoimmune diseases, allergies, infectious diseases and malignant tumors.