title: Dimeric MHC-peptides inserted into an immunoglobulin scaffold as new immunotherapeutic agents.
abstract: The interactions of the T cell receptor (TCR) with cognate MHC-peptide and co-stimulatory molecules expressed at surface of antigen presenting cells (APC) leads to activation or tolerance of T cells. The development of molecular biological tools allowed for the preparation of soluble MHC-peptide molecules as surrogate for the APC. A decade ago a monomeric class II MHC molecule in which the peptide was covalently linked to β-chain of class II molecule was generated. This type of molecule had a low-binding affinity and did not cause the multimerization of TCR. The requirement of multimerization of TCR led to development of a new class of reagents, chimeric peptides covalently linked to MHC that was dimerized via Fc fragment of an immunoglobulin and linked to 3' end of the β-chain of MHC class II molecule. These soluble dimerized MHC-peptide chimeric molecules display high affinity for the TCR and caused multimerization of TCR without processing by an APC. Because dimeric molecules are devoid of co-stimulatory molecules interacting with CD28, a second signal, they induce anergy rather the activation of T cells. In this review, we compare the human and murine dimerized MHC class II-peptides and their effect on CD4(+) T cells, particularly the generation of T regulatory cells, which make these chimeric molecules an appealing approach for the treatment of autoimmune diseases.
authors: Department of Chemistry, New York University, NY 10003-6688, USA. burt.goldberg@gmail.com
authors: Burt
authors: B
authors: Goldberg
authors: Constantin
authors: C
authors: Bona
mesh_terms: D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D055503:Protein Multimerization
chemical_list: D006680:HLA Antigens; D007136:Immunoglobulins; D010455:Peptides