Modulation of CD4 T cell function by soluble MHC II-peptide chimeras.
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 alpha-chain in the case of MHC I, or beta-chains in the case of MHC II molecules. Conceptually, such TCR/CD4 ligands shall provide the signal 1 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.
Casares
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Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Bona
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Brumeanu
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation; D017635:Clonal Anergy; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control; D000949:Histocompatibility Antigens Class II / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D051379:Mice; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction; D012995:Solubility
D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins