By Michael B. A. Oldstone
The conceptual foundation for molecular mimicry used to be first outlined within the early Nineteen Eighties whilst monoclonal antibodies opposed to viruses have been additionally proven to react with non-viral host protein; for that reason, measles virus phosphoprotein cross-reacted with host mobilephone cytokeratin, herpes simplex virus kind 1 with host-cell vimentin and vaccinia virus with host-cell intermediate filaments. Following this discovery, others emerged, back on the clonal point, that T telephone clones opposed to proteins from a number of infectious brokers additionally reacted with host antigenic determinants. The clonal contrast was once valuable for the preliminary definition of mimicry. at the least 30 years ahead of our preliminary description of molecular mimicry related to cross-reactions among a number of microbes, at the polyclonal antibody point, streptococcus used to be believed to react with renal glomeruli, middle and basal ganglia to account for the glomerulonephritis, center and valvular ailment and chorea, respectively. in spite of the fact that, next learn confirmed that the nephritis used to be brought on by immune complicated deposits and the tissue harm they produced. Later, in 1990, the cross-reactivity of streptococcal antigen with myocardial antigens on a clonal point used to be exposed. as a result, for either historic purposes and mechanistic figuring out, you must supply facts for cross-reactivity on the clonal point to end up that molecular mimicry exists.
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Extra info for Molecular Mimicry: Infection Inducing Autoimmune Disease
Identiﬁcation and analysis of two cross-reactive T cell epitopes within a single protein. J. Immunol. , Nicholson M. W. 2005. Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor. Nat. Immunol 6, 490–496. , Sinigaglia F. 1993. Promiscuous and allele-speciﬁc anchors in HLA-DR-binding peptides. W. 1999b. Peptide recognition by two HLA-A2/Tax11–19speciﬁc T cell clones in relationship to their MHC/peptide/TCR crystal structures. J. Immunol.
172:3893–3904 Carrizosa, AM, Nicholson, LB, Farzan, M, Southwood, S, Sette, A, Sobel, RA, and Kuchroo, VK (1998) Expansion by self antigen is necessary for the induction of experimental autoimmune encephalomyelitis by T cells primed with a crossreactive environmental antigen. J. Immunol.
Nevertheless, a number of different peptides can act as agonists for a given T cell and a considerably larger number of peptide ligands may induce weak signals, such as those that promote positive selection in the thymus and survival of naïve T cells in the periphery. TCR speciﬁcity and cross-reactivity thus represent important aspects of T cell biology. Acknowledgements I would like to acknowledge the important contributions that my colleagues and collaborators have made toward this research. In particular, I would like to acknowledge the contributions of Stefan Hausmann, Katherine Smith, Laurent Gauthier, Heiner Appel, Jason Pyrdol, David A.