Naked or peptide-clothed MHC?
Article Abstract:
The phenomena of cell rejection which takes place in failed organ transplants and bone grafts provides an opportunity to study cellular interactions. The molecular mechanism involved in this process was recently addressed in a conference in Milwaukee, Wisconsin. The focus of the conference was to develop a model of alloreactivity which conforms to both the actions which take place during the rejection process and in the observed molecular structures of the cell components. Alloreactivity refers to the immune response of cells to other cells of the same species which are composed of different genetic constituents. An example of this phenomena is the interaction of T lymphocytes and the cells that they target called the major histocompatibility complex (MHC), and the cells that they are stimulated by, which are the T-cell receptors. The primary area of discussion surrounded the specific nature of the T-cell receptor's composition. Specifically, theories on how the T-cell receptor interacts with the MHC molecule were debated. A variety of proposed models were presented and two opposing theories were discussed. It has been hypothesized that T-cell receptors react with the "naked" MHC, the molecule in its most simple form. Others argue that a reaction can occur only when the MHC molecule is complexed with a specific series of peptides (contain amino acids which make up proteins). The formation of a clear model of the mechanism of alloreactivity is difficult because the T-cell receptors are capable of a wide range of interactions. The model which was developed that received the most support incorporated aspects of both of these theories.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1989
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Invariant chain influences the immunological recognition of MHC class II molecules
Article Abstract:
The formation of complete class II major histocompatibility complex (MHC) antigens, which are recognized by CD4-positive T helper cells so that an immune response can be mounted, requires the association of the class II molecules with other MHC proteins known as invariant chains. This association of invariant chain molecules and MHC class II molecules may regulate the interaction between antigen molecules (which will be recognized by the immune system as foreign) and the MHC class II molecules. Cells not normally expressing MHC molecules were given the gene coding for MHC class II molecules either with or without the gene coding for the invariant chain molecules. It was shown that if the invariant chain is expressed, the cells can still process antigens (a procedure necessary for other cells to recognize foreign molecules) and present antigens to T helper cells, another step necessary for an immune response to occur. However, cells that do not contain the invariant chain express MHC class II molecules which are altered such that the cells have an increased ability to present antigenic peptides to T cells. Although the class II molecules are expressed in cells that do not contain the invariant chain, they bind less specific antibody molecules to MHC class II molecules, indicating that the structure of the protein is altered. The role of the invariant chain molecules in the presentation of antigens to cells of the immune system is not understood. These findings indicate that the invariant chain affects the shape of the MHC class II molecules at the cell surface. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1990
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An affinity for learning
Article Abstract:
The development of T lymphocytes into molecules that regulate the immune system and dysregulate protein expression depends on positive and negative selection by binding of major histocompatibility complex (MHC) molecules to agonists or antagonists. Agonist peptides bind to the MHC class I molecule (H-2K(super b)) and stimulate the sensitization of T cells for cytolysis. This causes negative selection and cell death of the T lymphocytes. Antagonist peptides bind to H-2K(super b) and oppose the effect of agonists. This causes positive selection and prevents cell death of the lymphocytes.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1996
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