02566nas a2200385   4500000000100000008004100001260001300042653001200055653002400067653001200091653002600103653001700129653002400146653001800170653003100188653001900219653003000238653003200268653001100300653002800311653001200339653002900351653003700380653002300417653002200440653002800462653001200490100001100502700001600513245009400529300001100623490000600634520152600640022001402166       1997                            d  c1997 Jun10aAlleles10aAmino Acid Sequence10aAnimals10aArthritis, Rheumatoid10aAutoantigens10aAutoimmune Diseases10aB-Lymphocytes10aCD4-Positive T-Lymphocytes10aChagas disease10aDiabetes Mellitus, Type 110aHistocompatibility Antigens10aHumans10aImmunodominant Epitopes10aleprosy10aLiver Cirrhosis, Biliary10aMajor Histocompatibility Complex10aModels, Biological10aMolecular Mimicry10aMolecular Sequence Data10aUveitis1 aBaum H1 aStaines N A00aMHC-derived peptides and the CD4+ T-cell repertoire: implications for autoimmune disease.  a115-250 v33 a<p>The receptor repertoire of peripheral CD4+ cells is primarily determined by selection processes in the thymus. These result in the positive selection of T cells whose receptors weakly recognize self-peptides restricted by class II self-MHC heterodimers. A majority of such self-peptide partial agonists are likely to be derived from self-MHC molecules. It is suggested that these thymically selected, weakly autoreactive T cells may subsequently be stimulated by peripheral exposure to microbially derived agonists that 'mimic' corresponding self-MHC peptides. In turn, 'molecular mimicry' between microbial agonists and tissue-specific self-peptides may lead to T-cell-mediated autoimmune disease. Hence such disease may reflect 'three-way mimicry' between peptides of respectively target tissue, pathogen and self-MHC (or other self-peptide dominantly presented in the thymus). This hypothesis accounts for the role of MHC haplotype in determining susceptibility to (or protection from) autoimmune disease. Direct evidence is presented in favour of the model as applied to diseases such as rheumatoid arthritis, autoimmune uveitus and autoimmune diabetes. Strong circumstantial evidence, based primarily on sequence similarities, is also presented for other autoimmune diseases. However, it is noted that the statistics of database searches, and the lack of predictable correlation between sequence similarity and T-cell cross-reactivity, require that such evidence be substantiated by further direct experiment.</p>  a1368-4736