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Infection and Immunity, September 1999, p. 4312-4319, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Identification of Amino Acid Residues of the T-Cell Epitope of Mycobacterium tuberculosis alpha  Antigen Critical for Vbeta 11+ Th1 Cells

Ai Kariyone,1 Kazue Higuchi,2 Shigeki Yamamoto,3 Ai Nagasaka-Kametaka,1 Mamoru Harada,4 Akio Takahashi,5 Nobuyuki Harada,2 Kazumasa Ogasawara,5 and Kiyoshi Takatsu1,*

Department of Immunology, Institute of Medical Science, University of Tokyo, Minato-ku,1 Research Institute of Tuberculosis, Kiyose,2 and National Institute of Public Health,3 Tokyo, Medical Institute of Bioregulation, Kyushu University, Fukuoka,4 and Institute of Immunology, Hokkaido University, Sapporo,5 Japan

Received 8 February 1999/Returned for modification 30 March 1999/Accepted 23 June 1999

Stimulation of Mycobacterium tuberculosis-primed lymph node cells from C57BL/6 mice with alpha  antigen (also known as antigen 85B and MPT59) induced cell proliferation, production of interleukin 2 and gamma interferon, and expansion of Vbeta 11+ CD4+ T cells in conjunction with antigen-presenting cells in an I-Ab-restricted manner. Using a series of 15-amino-acid peptides that overlapped each other by 5 amino acids and spanned the mature alpha  antigen, we identified the antigenic epitope for alpha  antigen-specific Vbeta 11+ Th1 cells. That peptide (peptide-25), which corresponds to amino acid residues 240 to 254 of alpha  antigen, contains a motif that is conserved in I-Ab and requires processing by antigen-presenting cells. Using peptide-25-reactive Vbeta 11+ T-cell clones and substituted peptide-25 mutants, we determined which amino acid residues within peptide-25 were critical for T-cell receptor (TCR) recognition. Our results showed that the amino acid residues at positions 245, 246, 248, 250, and 251 are important for recognition of TCRVbeta 11 and that residues at positions 244, 247, 249, and 252 are I-Ab contact residues. We also observed that active immunization of C57BL/6 mice with peptide-25 can lead to decreased bacterial load in the lungs of M. tuberculosis H37Rv-infected mice. These results should provide us with a useful tool for delineating the regulation of Vbeta 11+ Th1-cell development during M. tuberculosis infection and for developing a vaccine inducing a Th1-dominant immune response.

* Corresponding author. Mailing address: Department of Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-5449-5260. Fax: 81-3-5449-5407: E-mail: takatsuk{at}ims.u-tokyo.ac.jp.

Infection and Immunity, September 1999, p. 4312-4319, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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