Major histocompatibility complex proteins peptide presentation

Major-Histocompatibility-Complex Proteins Present Peptide Antigens on Cell Surfaces for Recognition by T-Cell Receptors... 

Major-Histocompatibility-Complex Proteins Present Peptide Antigens on Cell Surfaces for Recognition by T-Cell Receptors Intracellular pathogens such as viruses and mycobacteria cannot be easily detected. Intracellular proteins are constantly being cut into... 

Major-Histocompatibility-Complex Proteins Present Peptide Antigens... 

MAJOR-HISTOCOMPATIBILITY-COMPLEX PROTEINS PRESENT PEPTIDE ANTIGENS ON CELL SURFACES FOR RECOGNITION BY T-CELL RECEPTORS... 

Recognition. Antibodies are proteins that form part of the immrme response in manunals in the presence of foreign invaders. Other proteins form the major histocompatibility complex (MHC), which presents small peptides from viruses and other invaders for recognition by the immrme system. 

Group of transmembrane proteins engaged in the presentation of small peptide fragments to T-cells. Two classes of Major histocompatibility complex (MHC) molecules exist both of which are encoded by a highly polymorphic gene cluster. MHC class I and class II proteins present peptide fragments to CD8+ and CD4+ T-cells, respectively. The human MHC is also known as HLA, the murine MHC as H-2 complex. 

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). 

MHC class I and II proteins, the presenters of peptides to T cells, were discovered because of their role in transplantation rejection. A tissue transplanted from one person to another or from one mouse to another is usually rejected by the immune system. In contrast, tissues transplanted from one identical twin to another or between mice of an inbred strain are accepted. Genetic analyses revealed that rejection occurs when tissues are transplanted between individuals having different genes in the major histocompatibility complex, a cluster of more than 75 genes playing key roles in immunity. The 3500-kb span of the MHC is nearly the length of the entire E. coli chromosome. The MHC encodes class I proteins (presenters to cytotoxic T cells) and class II proteins (presenters to helper T cells), as well as class III proteins (components of the complement cascade) and many other proteins that play key roles in immunity. 

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). 

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