Class I MHC-peptide complex

Figure 33.30. T-Cell Activatiou. The interaction between the T-cell receptor and a class I MHC-peptide complex results in the binding of CDS to the MHC protein, the recruitment of the protein tyrosine kinase Lck, and the phosphorylation of tyrosine residues in the ITAM sequences of the CD3 chains. After phosphorylation, the ITAM regions serve as docking sites for the protein kinase ZAP-70, which phosphorylates protein targets to transmit the signal.

The T-cell receptor does not act alone in recognizing and mediating the fate of target cells. Cytotoxic T cells also express a protein termed CD8 on their surfaces that is crucial for the recognition of the class I MHC-peptide complex. The abbreviation CD stands for cluster of differentiation, referring to a cell-surface marker that is used to identify a lineage or stage of differentiation. Antibodies specific for particular CD proteins have been invaluable... 

I MHC-peptide complexes and those that recognize class 11 MHC-peptide complexes utilize the same set of Va and Vp genes, and the principal feature that defines the site of class 1 MHC-TCR interaction, the cleft formed by the a and az subunits of the MHC molecule, is shared by both class 1 and class... 

MHC-class I proteins Some microorganisms have developed a considerable number of tricks to interfere with the presentation of the MHC-class I protein peptide complex on the surface of the infected host cell for example, production of a protein that binds the MHC protein and causes it to be retained within the endoplasmic reticulum. 

Example Holtz and Folkers Exemplified the typical case of a major histocompatibility complex (MHC) poptide as depicted in Figures 6. It broadly and vividly shows the simplified model of binding of a nonapeptide i.e., having nine peptide linkages, to a Class I MHC-peptide as illustrated in HLA-B27. 

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. 

The groove can be filled by a peptide from 8 to 10 residues long in an extended conformation. As we shall see (Section 33.5.6). MHC proteins are remarkably diverse in the human population each person expresses as many as six distinct class I MHC proteins and many different forms are present in different people. The first structure determined, HLA-A2, binds peptides that almost always have leucine in the second position and valine in the last position (Figure 33.25). Side chains from the MHC molecule interact with the amino and carboxyl termini and with the side chains in these two key positions. These residues are often referred to as the anchor residues. The other residues are highly variable. Thus, many millions of different peptides can be presented by this particular class I MHC protein the identities of only two of the nine residues are crucial for binding. Each class of MHC molecules requires a unique set of anchor residues. Thus, a tremendous range of peptides can be presented by these molecules. Note that one face of the bound peptide is exposed to solution where it can be examined by other molecules, particularly T-cell receptors. An additional remarkable feature of MHC-peptide complexes is their kinetic stability once bound, a peptide is not released, even over a period of days. 

---