Adaptive and innate immunity have been implicated in the pathogenesis of atherosclerosis. Given their abundance in the lesion, lipids might be targets of the atherosclerosis-associated immune response. Natural killer T (NKT) cells can recognize lipid antigens presented by CD1 molecules. We have explored the role of CD1d-restricted NKT cells in atherosclerosis by using apolipoprotein E-deficient...

Immunophenotyping is indispensable in the differential diagnosis of B-cell chronic lymphoproliferative disorders (B-CLPDs). However, B-CLPDs often show overlapping immunophenotypic profiles and may be diagnostically challenging. CD1d is an HLA class I-like molecule that presents glycolipids to invariant natural killer T cells. Normal mature B cells constitutively express CD1d, but with the exce...

Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ1...

Ab that arise in the absence of T cell help are a critical host defense against infection with the spirochetes Borrelia burgdorferi and Borrelia hermsii. We have previously shown that CD1d-deficient (CD1d(-/-)) mice have impaired resistance to infection with B. burgdorferi. In mice, CD1d expression is highest on marginal zone B (MZB) cells, which produce Ab to blood-borne Ag. In this study we e...

Invariant natural killer T cells (iNKT cells) respond to CD1d-presented glycolipids from Borrelia burgdorferi, the causative agent of Lyme disease. Although mouse and human iNKT cells respond to different antigens based on subtle differences in their fatty acids, the mechanism by which fatty acid structure determines antigenic potency is not well understood. Here we show that the mouse and huma...

Invariant natural killer T (iNKT) cells are a subset of nonconventional T cells recognizing endogenous and/or exogenous glycolipid antigens in the context of CD1d molecules. It remains unclear whether innate stimuli can modify the profile of endogenous lipids recognized by iNKT cells on the surface of antigen-presenting cells (APCs). We report that activation of human APCs by Toll-like receptor...

Most NK1.1+ T (NKT) cells express a biased TCRalphabeta repertoire that is positively selected by the monomorphic MHC class I-like molecule CD1d. The development of CD1d-dependent NKT cells is thymus dependent but, in contrast to conventional T cells, requires positive selection by cells of hemopoietic origin. Here, we show that the Src protein tyrosine kinase Fyn is required for development of...

CD1d-restricted natural killer (NK)T cells are known to potently secrete T helper (Th)1 and Th2 cytokines and to mediate cytolysis, but it is unclear how these contrasting functional activities are regulated. Using lipid antigen-loaded CD1d tetramers, we have distinguished two subsets of CD1d-restricted T cells in fresh peripheral blood that differ in cytokine production and cytotoxic activatio...

B cell activation and Ab production in response to protein Ags requires presentation of peptides for recruitment of T cell help. We and others have recently demonstrated that B cells can also acquire innate help by presenting lipid Ags via CD1d to NKT cells. Given the newfound contribution of NKT cells to humoral immunity, we sought to identify the pathways that regulate CD1 molecule expression...

Invariant natural killer T cells (iNKTs) are innate-like T cells that are highly concentrated in the liver and recognize lipids presented on the MHC-like molecule CD1d. Although capable of a myriad of responses, few essential functions have been described for iNKTs. Among the many cell types of the immune system implicated in metabolic control and disease, iNKTs seem ideally poised for such a r...