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Infection and Immunity, October 2000, p. 5846-5855, Vol. 68, No. 10
Immunology Unit, Department of Infectious and
Tropical Diseases, London School of Hygiene and Tropical Medicine,
London WC1E 7HT,1 and Infectious
Diseases and Microbiology, Imperial College School of Medicine, St.
Mary's Campus, London W2 1PG,2 United Kingdom;
Armauer Hansen Research Institute, Addis Ababa,
Ethiopia3; Vaccines and Biologicals,
CH 1211, World Health Organization, Geneva 27, Switzerland4; Microbiology
Department, Aga Khan University, Karachi 74800, Pakistan5; Anandaban Leprosy
Hospital, Kathmandu, Nepal6;
Instituto de Inmunologia, Bogota,
Colombia7; and Leprosy Laboratory,
Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro,
Brazil8
Received 6 January 2000/Returned for modification 22 February
2000/Accepted 18 July 2000
To identify Mycobacterium leprae-specific human T-cell
epitopes, which could be used to distinguish exposure to M. leprae from exposure to Mycobacterium tuberculosis or
to environmental mycobacteria or from immune responses following
Mycobacterium bovis BCG vaccination, 15-mer synthetic
peptides were synthesized based on data from the M. leprae
genome, each peptide containing three or more predicted HLA-DR
binding motifs. Eighty-one peptides from 33 genes were tested for their
ability to induce T-cell responses, using peripheral blood mononuclear
cells (PBMC) from tuberculoid leprosy patients (n = 59) and healthy leprosy contacts (n = 53) from Brazil,
Ethiopia, Nepal, and Pakistan and 20 United Kingdom blood bank donors.
Gamma interferon (IFN-
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
A Postgenomic Approach to Identification of
Mycobacterium leprae-Specific Peptides as T-Cell
Reagents
and
) secretion proved more sensitive for
detection of PBMC responses to peptides than did lymphocyte
proliferation. Many of the peptides giving the strongest responses in
leprosy donors compared to subjects from the United Kingdom, where
leprosy is not endemic, have identical, or almost identical, sequences
in M. leprae and M. tuberculosis and would not
be suitable as diagnostic tools. Most of the peptides recognized by
United Kingdom donors showed promiscuous recognition by subjects expressing differing HLA-DR types. The majority of the novel T-cell epitopes identified came from proteins not previously recognized as
immune targets, many of which are cytosolic enzymes. Fifteen of the
tested peptides had 
5 of 15 amino acid mismatches between the
equivalent M. leprae and M. tuberculosis
sequences; of these, eight gave specificities of 90% (percentage of
United Kingdom donors who were nonresponders for IFN- secretion),
with sensitivities (percentage of responders) ranging from 19 to 47%
for tuberculoid leprosy patients and 21 to 64% for healthy leprosy
contacts. A pool of such peptides, formulated as a skin test reagent,
could be used to monitor exposure to leprosy or as an aid to early diagnosis.
*
Corresponding author. Mailing address: Immunology Unit,
Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. Phone: (44) 20 7927 2466. Fax: (44) 20 7637 4314. E-mail: hazel.dockrell{at}lshtm.ac.uk.
Present address: Department of Bacteriology, ID-Lelystad, 8200 AB
Lelystad, The Netherlands.
Infection and Immunity, October 2000, p. 5846-5855, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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