Andrew - here is some in depth knowledge covering all autoimmune disease based on MS but RA ans AS are the same mechanism, just different proteins and different genes -
The concept that molecular mimicry is an important factor in autoimmune disease was first published in 1985 and since that time substantial evidence has accumulated such that it has become the favoured mechanism for causing many autoimmune diseases including MS.
The concept is deceiving simple but entails a lot of understanding of the workings of the immune system. Basically molecular mimicry means that part of a molecule of a given protein closely resembles a part of another totally different protein. Proteins are made up of strings of amino acids and in molecular mimicry one series amino acids(eg~10) in one protein is very similar to a string of ten amino acids in another protein. Given that there are 20 different amino acids it is a rather rare occurrence to find such mimicking arrangements but many examples have been demonstrated.
The main types of proteins which came into play in autoimmune disease are:
self proteins which are part of the human body.An example of this would be myelin basic protein which is the most common protein in myelin;
proteins of infectious agents such as viruses and bacteria;
food proteins.For example over 400 different proteins occur in cow's milk and most have over 150 amino acids.
To understand how molecular mimicry works in the induction of autoimmunity one must understand the basic mechanisms of an immune response to a foreign invader in the body. The immune system recognizes a part of the protein portion of the invader. It does this with T cells which have receptors which bind to short segments(~10 amino acids) of a foreign protein. It is helped in this task by so called antigen presenting cells such as macrophages. A macrophage will engulf a foreign invader(eg a bacteria or food particle) and break it down into fragments. A special molecule in the macrophage then carries a protein fragment(peptide) to the surface of the cell and "presents" it to the millions of circulating T cells. A T cell which has a matching receptor locks onto the presented protein fragment. The T cell then becomes activated and stimulates other portions of the immune system to begin an immune response against all proteins which contain a similar looking amino acid string. The details of what constitutes a similar looking string are beyond this summary but suffice to say it has been found that a variety of similar, yet somewhat different strings, can be recognized by the same T cell.
Thus, it is easy to understand how molecular mimicry can trigger an autoimmune reaction. If the protein fragment from a foreign invader which is presented to the T cell closely resembles part of a self protein then the activated immune system will not only attack all foreign invaders which have the same string of amino acids but will also attack a very similar string in a self protein. It has been shown that parts of proteins in various foods and infectious agents resemble parts of various self proteins. Sometimes a three way mimicry occurs with a protein fragment from a food closely resembling that of an infectious agent which in turn closely resembles part of a self protein. In Celiac disease part of the gliadin molecule (found in various grains such as wheat and rye), part of adenovirus 12 and part of a gut protein all closely resemble each other and the result of such mimicry is an immune attack on the gut when food containing gliadin protein is eaten. A similar three way mimicry occurs between a cell wall protein in grains and legumes, part of the Epstein Barr virus and part of the collagen in joints. This leads to rheumatoid arthritis in genetically susceptible people. For type 1 diabetes parts of milk proteins and viral proteins mimic proteins in the insulin-producing beta cells of the pancreas.
For MS it has been established that numerous viruses and bacteria have amino acid strings which mimic parts of proteins in the myelin proteins of the central nervous system. Undoubtedly food proteins also contain such mimicking protein fragments and thus two and three way mimicry is a ready explanation for why the immune system attacks myelin and causes MS.
An important part of molecular mimicry is what exact string of amino acids is presented to the immune system because that will determine if part of a self protein is also mimicked or not. That is why MS and other autoimmune diseases are strongly dependent on genetic makeup and why only a small percentage of the population contracts these diseases. Most people do not have genes which result in mimicking peptides being presented to their immune system. A person's genes will also determine which self protein is mimicked and thus what specific autoimmune disease that person gets. People, who have genes such that a myelin protein is mimicked by a presented foreign protein fragment, will experience an immune attack on their myelin which eventually leads to clinical symptoms and a diagnosis of MS. Those who present collagen-mimicking fragments get rheumatoid arthritis.
Currently most researchers are concentrating on infectious agents as the main drivers of molecular mimicry despite the strong evidence that food proteins also supply appropriate mimics. In fact it is likely that food proteins are the main mimics in some cases because the geographical distribution of diseases such as MS and type 1 diabetes closely follows differences in dietary habits rather than differences in infectious agents. Of course it has been established that food proteins are the driver of Celiac disease, one of the few autoimmune diseases for which the cause is known.
In summary, molecular mimicry is currently the best explanation for why the immune system attacks self tissue in some people. When all is said and done it just comes down to a case of mistaken identity in which the immune system in genetically susceptible people mistakes part of the body for a foreign invader. Below are some medline abstracts on the concept of molecular mimicry.
