ABSTRACT
Science Immunology will provide a broad platform for the most exciting findings in this growing field.
ABSTRACT
Group 1 CD1 (CD1a, CD1b, and CD1c)-restricted T cells recognize mycobacterial lipid antigens and are found at higher frequencies in Mycobacterium tuberculosis (Mtb)-infected individuals. However, their role and dynamics during infection remain unknown because of the lack of a suitable small animal model. We have generated human group 1 CD1 transgenic (hCD1Tg) mice that express all three human group 1 CD1 isoforms and support the development of group 1 CD1-restricted T cells with diverse T cell receptor usage. Both mycobacterial infection and immunization with Mtb lipids elicit group 1 CD1-restricted Mtb lipid-specific T cell responses in hCD1Tg mice. In contrast to CD1d-restricted NKT cells, which rapidly respond to initial stimulation but exhibit anergy upon reexposure, group 1 CD1-restricted T cells exhibit delayed primary responses and more rapid secondary responses, similar to conventional T cells. Collectively, our data demonstrate that group 1 CD1-restricted T cells participate in adaptive immune responses upon mycobacterial infection and could serve as targets for the development of novel Mtb vaccines.
Subject(s)
Antigens, CD1/immunology , Immunity/immunology , Mycobacterium/immunology , Animals , Antigen Presentation/immunology , Cell Line , Dendritic Cells/cytology , Dendritic Cells/immunology , Epitopes , Humans , Immunization , Kinetics , Lipids/immunology , Lymphocyte Activation/immunology , Mice , Mice, Transgenic , Molecular Mimicry , Mycobacterium tuberculosis/immunology , Natural Killer T-Cells/cytology , Natural Killer T-Cells/immunology , Phenotype , T-Lymphocytes, Cytotoxic/immunology , Th1 Cells/immunologyABSTRACT
CD1 proteins constitute a distinct lineage of antigen-presenting molecules specialized for the presentation of lipid antigens to T cells. In contrast to the extensive sequence polymorphism characteristic of classical MHC molecules, CD1 proteins exhibit limited sequence diversity. Here, we describe the identification and characterization of CD1d alleles in wild-derived mouse strains. We demonstrate that polymorphisms in CD1d affect the presentation of endogenous and exogenous ligands to CD1d-restricted T cells, including type I (Valpha14i) and type II (non-Valpha14i) natural killer T (NKT) cells. Using congenic mice, we found CD1d polymorphisms affect the thymic selection of type I NKT cells and induce allogeneic T cell responses. Collectively, results from these studies demonstrate a role for polymorphisms in influencing the development and function of CD1d-restricted T cells.
