Dimeric MHC-peptides inserted into an immunoglobulin scaffold as new immunotherapeutic agents

作者：Goldberg Burt^*; Bona Constantin

来源：Journal of Cellular and Molecular Medicine, 2011, 15(9): 1822-1832.

DOI：10.1111/j.1582-4934.2011.01319.x

• dimeric class II-peptide molecules
• peptides derived from auto-antigens
• CD4 T cells
• Tr1 regulatory T cells
• interleukin-10

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 beta-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 beta-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.

• 出版日期2011-9