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.
The Leishmania major LACK antigen contains an immunodominant epitope at amino acids 156 to 173 (LACK(156-173)) 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 Vbeta4/Valpha8 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.
Kelly
Ben L
BL
Departmrnt of Medicine, Howard Hughes Medical Institute, University of California-San Francisco, UCSF Medical Center, Room C-443, 521 Parnassus Avenue, San Francisco, CA 94143-0654, USA.
Locksley
Richard M
RM
D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D016056:Immunodominant Epitopes; D015847:Interleukin-4 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology*
D000953:Antigens, Protozoan; D016056:Immunodominant Epitopes; D015800:Protozoan Proteins; C093139:LACK antigen, Leishmania; D015847:Interleukin-4