Polymorphisms in CD1d affect antigen presentation and the activation of CD1d-restricted T cells

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 t...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-02, Vol.106 (6), p.1909-1914
Main Authors: Zimmer, Michael I, Nguyen, Hanh P, Wang, Bin, Xu, Honglin, Colmone, Angela, Felio, Kyrie, Choi, Hak-Jong, Zhou, Ping, Alegre, Maria-Luisa, Wang, Chyung-Ru
Format: Article
Language:English
Subjects:
Alleles
Animals
Antigen Presentation - genetics
Antigens
Antigens, CD1d - genetics
Biological Sciences
Cell lines
Hybridomas
Killer Cells, Natural - immunology
Lipids
Lymphocyte Activation - genetics
Mice
Mice, Congenic
Molecules
Natural killer T cells
Polymorphism
Polymorphism, Genetic
Proteins
Rodents
Splenocytes
T cell antigen receptors
T cell receptors
T lymphocytes
T-Lymphocytes - immunology
Thymus Gland - immunology
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Summary: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 (Vα14i) and type II (non-Vα14i) 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0808476106