Structural requirements for binding of Myelin Basic Protein (MBP) Peptides to MHC II: effects on immune regulation

Mantzourani, Efthymia D. ORCID: https://orcid.org/0000-0002-6313-1409, Mavromoustakos, T. M., Platts, James Alexis ORCID: https://orcid.org/0000-0002-1008-6595, Matsoukas, J. M. and Tselios, T. V. 2005. Structural requirements for binding of Myelin Basic Protein (MBP) Peptides to MHC II: effects on immune regulation. Current Medicinal Chemistry 12 (13) , pp. 1521-1535. 10.2174/0929867054039053

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Abstract

Confronting Multiple Sclerosis requires as an underlying step the manipulation of immune response through modification of Myelin Basic Protein peptides. The aim is to design peptidic or nonpeptidic molecules that compete for recognition of self-antigens at the level of antigen presentation. The rational approach is to substitute residues that serve as anchors for the T-Cell Receptor with others that show no binding at all, and those that serve as Major Histocompatibility Complex II anchors with others that present increased binding affinity. The resulting structure, hence, retains normal or increased MHC II binding properties, but fails to activate disease-inducing T-cells. This rational design can only be achieved by identifying the structural requirements for binding of the natural peptide to MHC II, and the anchor residues with their corresponding specific pockets in the binding groove. The peptide-MHC II complex then interacts with the TCR; thus, an additional way to trigger the desired immune response is to alter secondary anchor residues as well as primary ones. In this review, the structural requirements for binding of MBP peptides to MHC II are presented, as are the mechanism and key features for TCR recognition of the peptide-MHC II complex.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	multiple sclerosis; myelin basic protein; mhc II; hla-dr; apl; bioactive conformation
Publisher:	Bentham Science Publishers
ISSN:	0929-8673
Last Modified:	19 Oct 2022 08:32
URI:	https://orca.cardiff.ac.uk/id/eprint/18099

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