Abstract:
:Invariant natural killer T cell (NKT) cells (iNKT cells) produce both T-helper 1 (Th1) and T-helper 2 cytokines in response to α-Galactosylceramide (α-GalCer) stimulation and are thought to be the important effectors in the regulation of both innate and adaptive immunity involved in autoimmune disorders, microbial infections, and cancers. However, the anticancer effects of α-GalCer were limited in early clinical trial. In this study, several analogs of α-GalCer, containing phenyl groups in the lipid tails were found to stimulate murine and human iNKT cells to secrete Th1-skewed cytokines and exhibit greater anticancer efficacy in mice than α-GalCer. We explored the possibility of different Vβ usages of murine Vα14 iNKT or human Vα24 iNKT cells, accounting for differential cytokine responses. However, T-cell receptor Vβ analysis revealed no significant differences in Vβ usages by α-GalCer and these phenyl glycolipid analogs. On the other hand, these phenyl glycolipids showed greater binding avidity and stability for iNKT T-cell receptor when complexed with CD1d. These findings suggest that CD1d-phenyl glycolipid complexes may interact with the same population of iNKT cells but with higher avidity and stability to drive Th1 polarization. Thus, this study provides a key to the rational design of Th1 biased CD1d reactive glycolipids in the future.
journal_name
Proc Natl Acad Sci U S Aauthors
Wu TN,Lin KH,Chang YJ,Huang JR,Cheng JY,Yu AL,Wong CHdoi
10.1073/pnas.1114255108subject
Has Abstractpub_date
2011-10-18 00:00:00pages
17275-80issue
42eissn
0027-8424issn
1091-6490pii
1114255108journal_volume
108pub_type
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