03071nas a2200409   4500000000100000008004100001260001300042653002700055653001100082653001200093653002500105653003200130100001700162700001700179700001800196700001400214700001200228700001200240700001500252700001400267700001500281700001500296700001800311700001200329700001600341700001400357700001300371700001400384700001400398245006000412856005900472300002800531490001300559050003200572520204300604022001402647       2000                            d  c2000 Dec10aEpitopes, T-Lymphocyte10aHumans10aleprosy10aMycobacterium leprae10aSensitivity and Specificity1 aDockrell H M1 aBrahmbhatt S1 aRobertson B D1 aBritton S1 aFruth U1 aGebre N1 aHunegnaw M1 aHussain R1 aManadhar R1 aMurrillo L1 aPessolani M C1 aRoche P1 aSalgado J L1 aSampaio E1 aShahid F1 aThole J E1 aYoung D B00aDiagnostic assays for leprosy based on T-cell epitopes.  uhttp://leprev.ilsl.br/pdfs/2000/v71s1/pdf/v71s1a11.pdf  aS55-8; discussion S58-90 v71 Suppl  aInfolep Library - available3 a<p>To date, only a limited number of antigens have been described as specific for Mycobacterium leprae, and in many cases, homologues have subsequently been shown to exist in mycobacteria such as M. avium and M. intracellulare. A Leprosy Synthetic Peptide Skin Test Initiative was established by the Steering Committee on the Immunology of Mycobacteria of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, to investigate the potential of synthetic peptides that encode T-cell epitopes as diagnostic tools, which could be used to develop a skin-test reagent specific for leprosy. Such M. leprae-specific peptides should have unique amino acid sequences, or significant sequence-dissimilarity from those in other mycobacteria. Synthetic peptides, 15 amino acids long, were synthesised from 33 genes or open reading frames within the M. leprae genome. Tuberculoid leprosy patients from four leprosy-endemic countries, Brazil, Ethiopia, Nepal and Pakistan, were tested as subjects known to have been infected with M. leprae, and to make good T-cell responses to antigens of M. leprae; UK blood donors were used as non-exposed or non-infected subjects. Peptides inducing potentially specific responses in leprosy patients and not in UK controls, and those inducing cross-reaction responses, present in both leprosy patients and non-exposed, non-infected controls, were identified. A difference from the equivalent M. tuberculosis sequence of five or more amino acid residues did not, by itself, identify peptides that were M. leprae-specific, suggesting that many of these peptides may have homologues in environmental mycobacteria. To date, this approach has identified a number of peptides with greater than 90% specificity and 19-47% sensitivity, which are undergoing further specificity-testing. Such peptides would have great potential as T-cell reagents with which to monitor exposure to M. leprae within communities, formulated either as skin-test reagents, or as antigens for tests in vitro.</p>  a0305-7518