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Infection and Immunity, November 1999, p. 5683-5689, Vol. 67, No. 11
Department of Microbiology, Faculty of
Medicine, Kuwait University, Safat, Kuwait1;
Institute of Transplantation Immunology, The National Hospital,
N-0027 Oslo, Norway2; Institute for
Animal Science and Health (ID-DLO), 8200 AB Lelystad, The
Netherlands3; Division of AIDS, STD, and
TB Laboratory Research, Centers for Disease Control and Prevention,
Atlanta, Georgia 303334; and
Department of Vaccinology, National Institute of Public
Health, N-0462 Oslo, Norway5
Received 9 April 1999/Returned for modification 7 June
1999/Accepted 5 August 1999
By using a synthetic peptide approach, we mapped epitopes from the
mycobacterial 65-kDa heat shock protein (HSP65) recognized by human T
cells belonging to the Mycobacterium leprae memory repertoire. A panel of HSP65 reactive CD4+ T-cell lines and
clones were established from healthy donors 8 years after immunization
with heat-killed M. leprae and then tested for
proliferative reactivity against overlapping peptides comprising both
the M. leprae and Mycobacterium tuberculosis
HSP65 sequences. The results showed that the antigen-specific T-cell lines and clones established responded to 12 mycobacterial HSP65 peptides, of which 9 peptides represented epitopes crossreactive between the M. tuberculosis and M. leprae HSP65
(amino acids [aa] 61 to 75, 141 to 155, 151 to 165, 331 to 345, 371 to 385, 411 to 425, 431 to 445, 441 to 455, and 501 to 515) and 3 peptides (aa 343 to 355, 417 to 429, and 522 to 534) represented
M. leprae HSP65-specific epitopes. Major histocompatibility
complex restriction analysis showed that presentation of 9 of the 12 peptides to T cells were restricted by one of the 2 HLA-DR molecules
expressed from self HLA-DRB1 genes, whereas 3 peptides with
sequences completely identical between the M. leprae and
M. tuberculosis HSP65 were presented to T cells by multiple
HLA-DR molecules: peptide (aa 61 to 75) was presented by HLA-DR1, -DR2,
and -DR7, peptide (aa 141 to 155) was presented by HLA-DR2, -DR7, and
-DR53, whereas both HLA-DR2 and -DR4 (Dw4 and Dw14) were able to
present peptide (aa 501 to 515) to T cells. In addition, the T-cell
lines responding to these peptides in proliferation assays showed
cytotoxic activity against autologous monocytes/macrophages pulsed with
the same HSP65 peptides. In conclusion, we demonstrated that
promiscuous peptide epitopes from the mycobacterial HSP65 antigen can
serve as targets for cytotoxic CD4+ T cells which belong to
the human memory T-cell repertoire against M. leprae. The
results suggest that such epitopes might be used in the peptide-based
design of subunit vaccines against mycobacterial diseases.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Identification of Promiscuous Epitopes from the
Mycobacterial 65-Kilodalton Heat Shock Protein Recognized by Human
CD4+ T Cells of the Mycobacterium leprae
Memory Repertoire
*
Corresponding author. Mailing address: Department of
Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. Phone: 965-5312300, ext. 6505. Fax: 965-5318454. E-mail: abusalim{at}hsc.kuniv.edu.kw.
Infection and Immunity, November 1999, p. 5683-5689, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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