Major histocompatibility complex MHC proteins

Formation of antigens from the intracellular degradation of pathogens The proteolytic system hydrolyses proteins of pathogens that are present within the host cell (e.g. a virus), to produce a short peptide which forms a complex with a specific protein, known as the major histocompatibility complex (MHC) protein. The peptide is, in fact, the antigen. At the plasma membrane, the MHC protein locates within the membrane and the small peptide sits on the outside of the membrane, where it can interact with the receptor on a cytotoxic T-lymphocyte to kill the host cell and the virus (Chapter 17). 

The requirement of multifunctional peptide complexes is perhaps most obvious for the development of subunit peptide vaccines. Successful immunizations with peptide antigens cannot be achieved without the inclusion of a bystander T-helper cell determinant in the chemical entity (4) or in the immunizing cocktail (5). For outbred animals and humans, multiple peptide epitopes, representing determinants of more than one major histocompatibility complex (MHC) proteins, are used to overcome subunit vaccine unresponsiveness, and this also improves antigen presentation in inbred animals (6). 

Major histocompatibility complex (MHC) proteins are essential components of the immune system (1). One speeific role is for them to bind and present cellularly derived peptides (-8-10 amino acids - MHC Class I peptides) at the cell surface. These peptides are subsequently challenged by cytolytic T-lymphocytes (CTL s) which are programmed to differentiate between self and exogenous peptides. T-cell recognition of these latter peptides initiates a response that ultimately results in cell lysis and death of the infected cell. Hence, structural characterization of such peptides could potentially result in the development of therapeutie treatments of a number of infectious disease states such as viral cancers, AIDS, and autoimmune disease. However, the task of sequencing such peptides is difficult since MHC class I proteins can bind and present 10,000-15,000 different cellularly derived peptides present at the sub-pieo-femtomole level (2,3). 

Epitopes for T lymphocytes comprise exclusively linear peptide sequences. T lymphocytes are unable to respond to carbohydrate, lipid or nucleic acid material and they only respond to peptide antigen when it is presented to the T lymphocyte by surface proteins on the plasma membrane of host cells. These surface proteins are termed major histocompatibility complex (MHC) proteins and can be subdivided into two main classes. MHC class I proteins are expressed on the surface of all nucleated host cell membranes and present peptide antigen to cytotoxic T lymphocytes. MHC class II proteins are expressed only on a more specialized group of cells termed antigen-presenting cells (APCs), and present peptide antigen to helper T lymphocytes. 

Also see color figure.) Major histocompatibility complex (MHC) proteins class II. The MHC class 11 proteins bind and present peptides that are synthesized outside the infected cell, i.e., peptides that are derived from proteins of the infecting organisms, bound to their specific T-cell receptors (TcRs). Interaction and stimulation of T-cell proliferation occurs with CDA" " T cells (Figure 35-16). The figure is derived from the coordinates published in the Protein Data Bank file 1A6A. 

CHAPTER 35, FIGURE 13 Major histocompatibility complex (MHC) proteins class I. The MHC class I proteins of antigen-presenting cells comprise two polypeptide chains, a and p. The a-polypeptide (-360 residues) (helices red,... 

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