Modulation of CD4 T cell function by soluble MHC II-peptide chimeras

• Published in: International reviews of immunology 2001, Vol.20 (5), p.547-573
• Main Authors: Casares, Sofia, Bona, Constantin A., Brumeanu, Teodor-Doru
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antigen Presentation; CD4 Antigens - metabolism; CD4 T cells; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation; Clonal Anergy; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - prevention & control; Histocompatibility Antigens Class II - pharmacology; Humans; Immunospecific modulation; Ligands; Mice; Models, Immunological; Receptors, Antigen, T-Cell - metabolism; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - pharmacology; Signal Transduction; Solubility; Soluble MHC II-peptide chimeras
• ISSN: 0883-0185; 1563-5244
• DOI: 10.3109/08830180109045578

Peptides antigens of 8 to 24 amino acid residues in length that are derived from processing of foreign proteins by antigen presenting cells (APC), and then presented to T cells in the context of major histocompatibility complex molecules (MHC) expressed by APC, are the only physiological ligands for T cell receptor (TCR). Co-ligation of TCR and CD4 co-receptor on T cells by MHC II-peptide complexes (signal 1) leads to various T cell functions depending on the nature of TCR and CD4 co-ligation, and whether costimulatory receptors (signal 2) such as CD28, CTLA-4, CD40L are involved in this interaction. Recently, the advance of genetic engineering led to the generation of a new class of antigen-specific ligands for TCR, i.e., soluble MHC class I, and MHC class II-peptide chimeras. In principle, these chimeric molecules consist of an antigenic peptide which is covalently linked to the amino terminus of α-chain in the case of MHC I, or β-chains in the case of MHC II molecules. Conceptually, such TCR/CD4 ligands shall provide the signal I to T cells. Since soluble MHC-peptide chimeras showed remarkable regulatory effects on peptide-specific T cells in vitro and in vivo, they may represent a new generation of immunospecific T cell modulators with potential therapeutic applicability in autoimmune and infectious diseases. This review is focused on the immunomodulatory effects of soluble, MHC class II-peptide chimeras, and discuss these effects in the context of the most accepted theories on T cell regulation.