Class peptide binding

Figure 15.19 Schematic representation of the peptide-binding domain of a class I MHC protein. The al and a2 domains are viewed from the top of the molecule, showing the empty antigen-binding site as well as the surface that is contacted by a T-cell receptor. (Adapted from P.J. Bjdrkman et al.. Nature 329 506-512, 1987.)...

Class 1 and class II MHC molecules bind peptide antigens and present them at the cell surface for interaction with receptors on T cells. The extracellular portion of these molecules consists of a peptide-binding domain formed by two helical regions on top of an eight-stranded antiparallel p sheet, separated from the membrane by two lower domains with immunoglobulin folds. These domains are differently disposed between the two protein subunits in class I and class II molecules. 

Murthy, V.L., 5tern, L.J. The class II MHC protein HLA-Drl in complex with an endogenous peptide implications for the structural basis of the specificity of peptide binding. Structure 5 1385-1396, 1997. 

F. F. Major histocompatibility complex class 11 binding characteristics of peptoid-peptide hybrids. Bioorg. Med. Chem. 

These T cells recognize peptide antigens bound to Class 1 MHC molecules on the surface of the target cell. During viral infections, viral peptides bind to selfMHCl molecules and are subsequently expressed on the cell surface. The MHCl molecules of transplanted tissues are themselves recognized by the Tc cells. 

Park, B., Lee, S., Kim, E., and Ahn, K. (2003) A single polymorphic residue within the peptide-binding cleft of MHC class I molecules determines spectrum of tapasin dependence. /. Immunol. 170, 961. 

Predicting binding affinities of protein ligands from three-dimensional models application to peptide binding to Class I major histocompatibility proteins. 

There are a number of MHC class I and class II polymorphic molecules, all with substantially the same basic structure. The MHC class I molecule is a dimer consisting of a glycoslylated transmembrane peptide of molecular weight 45 kDa covalently linked to a 12 kDa peptide it is found on the surface of most nucleated cells within the body. It is believed that the polypeptide backbones fold in such as way as to form a platform of -pleated sheet structures to support a peptide binding cleft in which the antigen fragments are held and presented to the T cells. 

Enfuvirtide (formerly called T-20) is a newly approved antiretroviral agent of a novel class, ie, a fusion inhibitor that blocks entry into the cell. Enfuvirtide, a synthetic 36-amino-acid peptide, binds to the gp41 subunit of the viral envelope glycoprotein, preventing the conformational changes required for the fusion of the viral and cellular membranes. 

Wang P, Sidney J, Dow C et al (2008) A systematic assessment of MHC class II peptide binding predictions and evaluation of a... 

Gowthaman U, Agrewala JN (2008) In silico tools for predicting peptides binding to HLA-class II molecules more confusion than conclusion. J Proteome Res 7 154-163... 

Christinck ER, Luscher MA, Barber BH, Williams DB. Peptide binding to class I MHC on living cells and quantitation of complexes required for CTL lysis. Nature 1991 352(6330) 67-70. 

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