T cells responsive to myelin basic protein in patients with multiple sclerosis

Article Abstract:

Many researchers now believe that multiple sclerosis (MS), a debilitating nervous system disorder, is an autoimmune disease, a condition where certain cells in the body attack the body's own tissues. The chief characteristic of MS is a loss of the protein myelin, which forms a sheath that surrounds nerves throughout the body and insulates them to ensure they will conduct electrical impulses in the appropriate manner. When myelin is gone, nerve conduction is abnormal and the impairments associated with MS appear. It is possible that an MS patient, for reasons that are not known, mounts an autoimmune response against his own myelin, in particular, one of the proteins associated with myelin, myelin basic protein (MBP). A sign that an immune response to a substance has occurred is the increased multiplication (proliferation) of a person's T cells when tested by exposure to the substance under laboratory conditions. This is called 'reactivity'. If MS patients have developed heightened immunity to MBP, their T cells would therefore be expected to show abnormal reactivity, but this has not been found in other experiments. It is possible, however, that mutant T cells in MS patients, normally only a small minority of the T cell population, are abnormally reactive. An autoimmune response with its accompanying increased rate of T cell division should lead to an increased number of mutations in T cells, since mutations increase as a function of the rate of replication. Thus, it was anticipated that the MS patients would have more mutant T cells, and this was found to be the case. In addition, several of these mutant clones demonstrated increased reactivity to MBP, an apparently autoimmune response. Evidence from this study supports the hypothesis that MS is associated with an autoimmune response against one's own myelin basic protein. (Consumer Summary produced by Reliance Medical Information, Inc.)

Causes of, Multiple sclerosis, Myelin proteins, Demyelinating diseases

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Antigen presentation requires transport of MHC class I molecules from the endoplasmic reticulum

Article Abstract:

Cytotoxic T lymphocytes (CTLs) are one subtype of T lymphocyte, or white blood cell, important in the body's defense against invasion. In order to successfully fight a foreign particle or molecule (called an antigen), however, the CTL must first recognize that it is foreign and not part of the animal's own body. This process is facilitated by another class of molecules called the major histocompatibility complex (MHC) molecules, class I, which must form a chemical complex with the antigen before the T cell can recognize it. MHC molecules are said to 'present' antigen to the CTL. But exactly where and at what point in the immune response the class I molecules link up with the antigen they will present has not been determined. A protein likely to be involved in antigen presentation is called E19 and is located on the endoplasmic reticulum (ER), an extensive network of tubules located in the cell cytoplasm where proteins are synthesized and transported. E19 is known to bind class I molecules and prevent them from leaving the ER. When levels of E19 were increased using experimental techniques, it appeared that some antigens (vaccinia and influenza virus proteins) were presented to the CTLs at a lower rate. This inhibition of presentation was correlated with reduced transport of class I molecules out of the ER, suggesting that such transport is the important step for antigen presentation. The results strengthen the likelihood that linkage between class I molecules and antigen occurs within the endoplasmic reticulum. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Endoplasmic reticulum, MHC antibodies

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Immuno-PCR with a commercially available aviden system

Article Abstract:

An antigen detection system that uses a biotinylated antibody and an avidin-biotinylated DNA complex is described. Commercially available aviden is used. The advantages and disadvantages of the system are described.

Immune recognition

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