International Immunology, Vol 9, 227-237, Copyright © 1997 by Oxford University Press
S Yanagisawa, M Koike, A Kariyone, S Nagai and K Takatsu
Antigenic epitopes for Mycobacterium tuberculosis-reactive T cell immune
responses have been mapped using the purified Mycobacterium protein
antigen. Lymph node cells from C57BL/6 mice that had been immunized with
heat-killed M. tuberculosis were cultured with various Mycobacterium
protein antigens and their reactivity was monitored by proliferative
response. Usage of the TCR beta chain repertoire was analyzed by flow
cytometry. Stimulation of M. tuberculosis-primed lymph node cells with
MPT59 (antigen 85B, alpha antigen) induced proliferative response,
production of IL-2 and IFN-gamma, and the expansion of V beta 11+ CD4+ T
cells in conjunction with antigen- presenting cells in an I-Ab-restricted
manner. Lymph node cells from non-primed mice failed to proliferate in
response to MPT59. Using peptides covering the complete mature 285 amino
acids long MPT59 protein as 15-mer molecules overlapping by five amino
acids, we identified the antigenic epitope for MPT59-specific V beta 11+ T
cells. The 15-mer peptide, covering amino acid residues 240-254 of MPT59
[peptide-25 (amino acids 240-254)], contains the motif that is conserved
for I-Ab and requires processing by antigen-presenting cells to trigger
peptide-25-specific V beta 11+ CD4+ T cells. We conclude from these results
that MPT59 and peptide-25 (amino acids 240-254) are not superantigens and
require antigen processing in order to stimulate V beta 11+ Th1 cells. This
experimental system will provide us with a useful tool for delineating the
regulation of T cell development in a particular subset of M. tuberculosis
infection and for developing antigenic peptides for Th1-dominant immune
responses.
ARTICLES
Mapping of V beta 11+ helper T cell epitopes on mycobacterial antigen in mouse primed with Mycobacterium tuberculosis
Department of Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
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