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Infection and Immunity, December 2004, p. 6924-6931, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6924-6931.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Leishmania major LACK Antigen with an Immunodominant Epitope at Amino Acids 156 to 173 Is Not Required for Early Th2 Development in BALB/c Mice

Ben L. Kelly and Richard M. Locksley*

Departments of Medicine and Microbiology/Immunology, Howard Hughes Medical Institute, University of California—San Francisco, San Francisco, California

Received 13 July 2004/ Returned for modification 22 August 2004/ Accepted 5 September 2004

The Leishmania major LACK antigen contains an immunodominant epitope at amino acids 156 to 173 (LACK156-173) that is believed to nucleate the pathological Th2 immune response in susceptible BALB/c mice. To test this hypothesis, we generated L. major parasites that express a mutated LACK that fails to activate Vß4/V{alpha}8 T-cell receptor transgenic T cells specific for this epitope. Although mutant parasites attenuated the expansion of endogenous LACK-specific, interleukin-4 (IL-4)-expressing, CD4 T cells compared to wild-type parasites in vivo, the overall frequency of IL-4 and gamma interferon-secreting lymphocytes was similar to that elicited by wild-type L. major. Mutant parasites demonstrated diminished amastigote viability and delayed lesion development in mice, although parasites could be recovered over 200 days after infection. Complementation with a wild-type lack fusion construct partially rescued these defects, indicating a role for endogenous LACK in parasitism. Mice inoculated with mutant parasites were not protected against subsequent infection with wild-type L. major.

* Corresponding author. Mailing address: UCSF Medical Center, Room C-443, 521 Parnassus Ave., San Francisco, CA 94143-0654. Phone: (415) 476-5859. Fax: (415) 476-9364. E-mail: locksley{at}medicine.ucsf.edu.

Editor: J. D. Clements

Infection and Immunity, December 2004, p. 6924-6931, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6924-6931.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Suzue, K., Kobayashi, S., Takeuchi, T., Suzuki, M., Koyasu, S. (2008). Critical role of dendritic cells in determining the Th1/Th2 balance upon Leishmania major infection. Int Immunol 20: 337-343 [Abstract] [Full Text]  


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