期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 7, 页码 1886-1892出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201141821
关键词
Antigen processing; presentation; CD1 molecules; NKT cell; Niemann-Pick type C disease
类别
资金
- MRC [G0700851, G0800158]
- Action Medical Research [SP4023]
- Niemann-Pick Disease Group UK
- SOAR-NPC
- Cancer Research UK [C399/A2291]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Office of Rare Diseases
- APMRF
- DART
- MRC [G0800158, G0700851, MC_UU_12010/1] Funding Source: UKRI
- Cancer Research UK [11331] Funding Source: researchfish
- Medical Research Council [G0800158, MC_UU_12010/1, G0700851] Funding Source: researchfish
Invariant natural killer T (iNKT) cells are a specialised subset of T cells that are restricted to the MHC class I like molecule, CD1d. The ligands for iNKT cells are lipids, with the canonical superagonist being a-galactosylceramide, a non-mammalian glycosphingolipid. Trafficking of CD1d through the lysosome is required for the development of murine iNKT cells. Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by dysfunction in either of two lysosomal proteins, NPC1 or NPC2, resulting in the storage of multiple lipids, including glycosphingolipids. In the NPC1 mouse model, iNKT cells are virtually undetectable, which is likely due to the inability of CD1d to be loaded with the selecting ligand due to defective lysosomal function and/or CD1d trafficking. However, in this study we have found that in NPC1 patients iNKT cells are present at normal frequencies, with no phenotypic or functional differences. In addi-tion, antigen-presenting cells derived from NPC1 patients are functionally competent to present several different CD1d/iNKT-cell ligands. This further supports the hypothesis that there are different trafficking requirements for the development of murine and human iNKT cells, and a functional lysosomal/late-endosomal compartment is not required for human iNKT-cell development.
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