Molecular Mimicry: Infection Inducing Autoimmune Disease (Current Topics in Microbiology and Immunology Book 296)

The purpose of this review is to examine the potential role of molecular mimicry in the pathogenesis of human T-lymphotropic virus type 1 ((HTLV- 1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)). Comp- hensive reviews on the pathogenic mechanisms of HTLV-1-associated human diseases are available throughout the medical literature (Bangham 2000,, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Osame 2002). Approximately 25 years ago the ?rst human retrovirus, HTLV-1, was isolated (Poeisz et al. 1980). Subsequently, infection with HTLV-1 was shown to cause adult T-cell leukemia (ATL) and HAM/TSP (Gessain et al. 1985; McFarlin and Blattner 1991; Osame et al. 1986; Poeisz et al. 1980; Yoshida et al. 1987). HTLV-1 may infect up to 30% of people in endemic areas and 10–20 million people worldwide (Barmak et al. 2003; Edlich et al. 2000). However, only 1%–5% develop either ATL or HAM/TSP, the remainder being clinically asymptomatic carriers of HTLV-1 (Bangham 2000, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Osame 2002). Why infection with HTLV-1 causes ATL or HAM/TSP in some people while the vast majority of individuals are asymptomatic is largely - known. Some possible factors that may differentiate the asymptomatic from the diseased state include viral strain, human histocompatibility leukocyte antigen (HLA), viral load, and the immune response (Bangham 2000, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Nagai et al. 1998; Niewiesk et al. 1994; Osame 2002). The conceptual basis for molecular mimicry was first defined in the early 1980s when monoclonal antibodies against viruses were also shown to react with non-viral host protein; in this case, measles virus phosphoprotein cross-reacted with host cell cytokeratin, herpes simplex virus type 1 with host-cell vimentin and vaccinia virus with host-cell intermediate filaments. Following this discovery, others emerged, again at the clonal level, that T cell clones against proteins from a variety of infectious agents also reacted with host antigenic determinants. The clonal distinction was imperative for the initial definition of mimicry. At least 30 years prior to our initial description of molecular mimicry involving cross-reactions between numerous microbes, on the polyclonal antibody level, streptococcus was believed to react with renal glomeruli, heart and basal ganglia to account for the glomerulonephritis, heart and valvular disease and chorea, respectively. However, subsequent research showed that the nephritis was caused by immune complex deposits and the tissue damage they produced. Later, in 1990, the cross-reactivity of streptococcal antigen with myocardial antigens on a clonal level was uncovered. Hence, for both historical reasons and mechanistic understanding, it is best to provide evidence for cross-reactivity at the clonal level to prove that molecular mimicry exists. Molecular Mimicry, Microbial Infection, And Autoimmune Disease : Evolution Of The Concept / M.b.a. Oldstone -- The Structural Interactions Between T Cell Receptors And Mhc-peptide Complexes Place Physical Limits On Self-nonself Discrimination / K.w. Wucherpfennig -- A Virus-induced Molecular Mimicry Model Of Multiple Sclerosis / J.k. Olson, A.m. Ercolini, And S.d. Miller -- Suppression Of Autoimmunity Via Microbial Mimics Of Altered Peptide Ligands / L. Steinman, P.j. Utz, And W.h. Robinson -- Molecular And Cellular Mechanisms, Pathogenesis, And Treatment Of Insulin-dependent Diabetes Obtained Through Study Of A Transgenic Model Of Molecular Mimicry / M.b.a. Oldstone. Trypanosoma Cruzi-induced Molecular Mimicry And Chagas' Disease / N. Gironès, H. Cuervo, And M. Fresno -- Htlv-1 Induced Molecular Mimicry In Neurological Disease / S.m. Lee ... [et Al.] -- Molecular Mimicry : Anti-dna Antibodies Bind Microbial And Nonnucleic Acid Self-antigens / J.s. Rice ... [et Al.] -- Chlamydia And Antigenic Mimicry / K. Bachmaier And J.m. Penninger. M.b.a. Oldstone (ed.). Includes Bibliographical References And Index. "Molecular mimicry as a pathogenic mechanism for understanding and developing insights into therapies for autoimmune disease was first presented in the early 1980s. By the end of the 1980s, sufficient reports occurred to publish a Current Topics in Microbiology and Immunology volume (vol. 145, 1989) focusing on the developing evidence for or against molecular mimicry as a cause of autoimmunity. In the ensuing years a plethora of reports using experimental models and studying human diseases have surfaced to firmly establish the concept and its potential role in several autoimmune disorders. This current volume selects several of these examples of molecular mimicry from recognized experts, who present their original findings. In addition, chapters on the evolution of the concept, its strengths and weaknesses are included in this volume."--BOOK JACKET