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ß T Cell Repertoire1
,
,§,,§
*
Department of Medicine, Committee on Immunology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637; Departments of
Medicine and
Microbiology and Immunology, and
§
Howard Hughes Medical Institute, University of California, San Francisco, CA 94143; and
¶
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104
Little is known regarding the diversity of the host T cell response
that is required to maintain immunologic control of microbial
pathogens. Leishmania major persist as obligate
intracellular parasites within macrophages of the mammalian host.
Immunity is dependent upon activation of MHC class II-restricted T
cells to an effector state capable of restricting growth and
dissemination of the organisms. We generated 
-ß
Leishmania-specific (ABLE) TCR transgenic mice with MHC
class II-restricted T cells that recognized an immunodominant
Leishmania Ag designated LACK. Naive T cells from ABLE mice
proliferated in vitro after incubation with recombinant LACK or with
Leishmania-parasitized macrophages and in vivo after
injection into infected mice. Infected ABLE mice controlled
Leishmania infection almost as well as wild-type mice
despite a drastic reduction in the T cell repertoire. ABLE mice were
crossed to mice with disruption of the TCR constant region gene to
create animals with a single ß T cell repertoire. Although mice
deficient in all ß T cells (TCR-Co mice) failed to
control L. major, mice with a monoclonal ß T cell
repertoire (ABLE TCR-Co mice) displayed substantial
control. The immune system is capable of remarkable efficiency even
when constrained to recognition of a single epitope from a complex
organism.
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