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Infection and Immunity, March 1999, p. 1501-1504, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Specificity and Function of Immunogenic Peptides from the 35-Kilodalton Protein of Mycobacterium leprae

Robert John Wilkinson,1,2,3 Katalin Andrea Wilkinson,1 Stipo Jurcevic,1 Adrian Hills,1 Sudhir Sinha,4 Utpal Sengupta,5 Diana N. J. Lockwood,6 Kiran Katoch,5 Daniel Altman,1 and Juraj Ivanyi1,*

MRC Clinical Sciences Center, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN,1 Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, London W1,6 and Wellcome Center for Clinical Tropical Medicine, Imperial College School of Medicine, Northwick Park Hospital, Harrow HA1 3UJ,2 United Kingdom, and National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067,3 Division of Membrane Biology, Central Drug Research Institute, Lucknow 226001,4 and Central Jalma Institute for Leprosy, Taj Ganj, Agra 282001,5 India

Received 20 October 1998/Returned for modification 8 December 1998/Accepted 21 December 1998

We identified a T-cell determinant of the 35-kDa antigen of Mycobacterium leprae which is discriminatory against cross-sensitization by its closely related homologue in Mycobacterium avium. From synthetic peptides covering the entire sequence, those with the highest affinity and permissive binding to purified HLA-DR molecules were evaluated for the stimulation of proliferation of peripheral blood mononuclear cells (PBMCs) from leprosy patients and healthy sensitized controls. Responses to the peptide pair 206-224, differing by four residues between M. leprae and M. avium, involved both species-specific and cross-reactive T cells. Lymph node cell proliferation in HLA-DRB1*01 transgenic mice was reciprocally species specific, but only the response to the M. leprae peptide in the context of DR1 was immunodominant. Of the cytokines in human PBMC cultures, gamma interferon production was negligible, while interleukin 10 (IL-10) responses in both patients and controls were more pronounced. IL-10 was most frequently induced by the shared 241-255 peptide, indicating that environmental cross-sensitization may skew the response toward a potentially pathogenic cytokine phenotype.

* Corresponding author. Present address: Department of Oral Medicine & Pathology, Floor 28, Guy's Tower, GKT School of Medicine & Dentistry, Guy's Hospital, London SE1 9RT, United Kingdom. Phone: 44 171 955 4256. Fax: 44 171 955 4455. E-mail: j.ivanyi{at}umds.ac.uk.

Infection and Immunity, March 1999, p. 1501-1504, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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