Molecular mimicry alone may not be able to induce disease; priming of the immune system by infection with a pathogen that carries a molecular mimic to self may have to be followed by a later nonspecific immunologic challenge in order for disease to be initiated

Molecular mimicry alone may not be able to induce disease; priming of the immune system by infection with a pathogen that carries a molecular mimic to self may have to be followed by a later nonspecific immunologic challenge in order for disease to be initiated. molecular mimic to a CNS antigen, may explain the inability of investigators to link one specific computer virus to MS. Molecular mimicry may be mediated through human leukocyte antigen class I\ and class II\restricted T cells and antibodies, which may explain the diversity in phenotype. Aspects of molecular mimicry will be discussed in relation to each of these immune system components. Examples of various molecular mimics will be discussed with a particular focus on the CNS and MS. Molecular mimicry alone may not be able to induce disease; priming of the immune system by infection with a pathogen that carries a molecular mimic to self may have to be followed by a later nonspecific immunologic challenge in order for disease to be initiated. Recent research into this priming and triggering of disease Mouse monoclonal to beta Tubulin.Microtubules are constituent parts of the mitotic apparatus, cilia, flagella, and elements of the cytoskeleton. They consist principally of 2 soluble proteins, alpha and beta tubulin, each of about 55,000 kDa. Antibodies against beta Tubulin are useful as loading controls for Western Blotting. However it should be noted that levels ofbeta Tubulin may not be stable in certain cells. For example, expression ofbeta Tubulin in adipose tissue is very low and thereforebeta Tubulin should not be used as loading control for these tissues will be discussed in relation to an animal model for MS. I.?Introduction Multiple sclerosis (MS) is the most common demyelinating disease in humans. MS has prevalence rates between 50 and 100 per 100,000 Caucasians; other ethnic groups have somewhat lower prevalence rates and women are more afflicted than men by a 2:1 ratio (Kurtzke, 1997). The inflammatory demyelinating lesions characteristic of MS are limited to the central nervous system (CNS) (Dejong, 1970). In most instances, MS patients have oligoclonal immunoglobulin (Ig)G bands in the cerebral spinal fluid (CSF), and a moderate mononuclear pleocytosis may also be present. Clinical features of the disease include vision loss, motor and sensory disturbances, and cognitive impairment. The clinical course of MS can include relapses and remissions and may be progressive in nature. MS has been proposed to be mediated by autoreactive CNS\specific CD4+ T cells (Markovic\Plese 2001, Noseworthy 2000). However, significant numbers of CD8+ T cells are found in MS lesions (Hayashi 1988, Sobel 1989) and are likely to be involved in pathogenesis. There have been many studies which attribute the neuroinflammation and neurodegeneration in MS to CD8+ T cells, CD4+ T cells, or antibody recognition of self. In this chapter, we summarize some salient points on each of these components of the immune system as they relate to molecular mimicry and disease. However, first we will provide Bivalirudin TFA background information and define molecular mimicry in relation to other key concepts. Molecular mimicry was first hypothesized to be a potential mechanism for the initiation of autoimmune disease in the early 1980s. It is said to occur when peptides from viral (Fujinami polymerase and the encephalitogenic epitope of myelin basic protein (MBP) for the rabbit could induce an experimental autoimmune encephalomyelitis (EAE)\like disease when used as an immunogen. For EAE to occur, this cross\reaction had to occur at the level of induction/activation of autoreactive CD4+ T cells. This was the first demonstration of autoimmune disease induced by a viral peptide (Fujinami and Oldstone, 1985). In the past, peptide similarities had been identified by computer searches for comparable amino acid sequences; however, based on more recent studies, molecular mimicry has also been shown to occur with incomplete sequence matching provided the major histocompatibility complex (MHC) and T\cell receptor (TCR) contact motifs are preserved (Lang (2002) suggested that molecular mimicry occurs rather frequently Bivalirudin TFA having shown that different peptides bound to class II molecules can lead to cross\reactivity by the same TCR provided the complexes have Bivalirudin TFA comparable charge distribution and overall shape. The flexibility of TCR recognition plays a major role in forming the T\cell repertoire through thymic selection, and is highly important in protecting the host against potential pathogen\derived antigens that are more wide ranging than the limited number of memory T cells (Casrouge 4\carboxymuconolactone decarboxylasea(Lenz polymerase (Fujinami \carboxymucono lactone decarboxylaseaMyelin oligodendrocyte glycoproteinButyrophilinfRubellagMyelin proteolipid proteinserine protease IV (Croxford (2003). bUfret\Vincenty (1998). cBoucher (2001). dCirone (2002). eDavies (1996). fStefferl (2000). gBesson Duvanel (2001). The Welsh and Selin laboratories have investigated molecular mimicry, or the sharing of immunologic cross\reactive epitopes, between viruses, as opposed to between a pathogen and its host, using such viruses as (LCMV), (PV), (VV), and murine cytomegalovirus (MCMV) (Brehm 2002, Chen 2001, Welsh 2000). They coined the term heterologous immunity to describe.