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Glycosylceramides in mammalian species are thought to be present in the form of β-anomers. This conclusion was reinforced by the identification of only one glucosylceramide and one galactosylceramide synthase, both β-transferases, in mammalian genomes. Thus, the possibility that small amounts of α-anomers could be produced by an alternative enzymatic pathway, by an unfaithful enzyme, or spontaneously...
Coreceptor CD4 and CD8αβ double-negative (DN) TCRαβ + intraepithelial T cells, although numerous, have been greatly overlooked and their contribution to the immune response is not known. Here we used T cell receptor (TCR) sequencing of single cells combined with retrogenic expression of TCRs to study the fate and the major histocompatibility complex (MHC) restriction of DN TCRαβ + ...
How do CD1 molecules load lipid antigens? In this issue of Immunity, Relloso et al. (2008) uncover how lysosomal pH targets amino acids in CD1b, causing it to open and attain a conformation more receptive to lipid antigens.
De Libero et al. (2005) demonstrate in this issue of Immunity that bacterial infection leads to increased synthesis of autologous glycolipids that are recognized by CD1-restricted human T cells, indicating that recognition of inducible self-glycolipids could be a mechanism for microbial detection. This mechanism also may provide a connection between infection and autoimmunity.
TL is a nonclassical MHC class I molecule that modulates T cell activation through relatively high-affinity interaction with CD8αα. To investigate how the TL/CD8αα interaction influences TCR signaling, we characterized the structure of the TL/CD8αα complex using X-ray crystallography. Unlike antigen-presenting molecules, the TL antigen-binding groove is occluded by specific conformational changes...
The origin and specificity of αβ TCR + T cells that express CD8αα have been controversial issues. Here we provide direct evidence that precursors of functional CD8αα T cells are positively selected in the thymus in the presence of agonist self-peptides. Like conventional positive selection, this agonist selection process requires functional TCR α-CPM, whereas it is independent of CD8β expression...
An aberrant T cell response to enteric bacteria is important in inflammatory bowel disease. However, the identity of relevant microbial antigens is unknown. Here, we report the presence of I2, a Crohn's disease-associated microbial gene, in the murine intestine. The I2 protein induced a proliferative and IL-10 response by CD4 + T cells from unimmunized mice. The I2 response was dependent on...
The structural basis for the T cell recognition of lipoglycans remains to be elucidated. We have described autoreactive T cells responsive to GM1 ganglioside presented by CD1b. We show that glycosphingolipids bind to CD1b on the cell surface at neutral pH and are recognized without internalization or processing. Furthermore, soluble GM1-CD1b complexes stimulate specific T cells. Oligosaccharide groups...
The ability of human CD1b molecules to present non- peptide antigens is suggested by the T cell recognition of microbial lipids and lipoglycans in the presence of CD1b-expressing antigen-presenting cells. We demonstrate the high-affinity interaction of CD1b molecules with the acyl side chains of known T cell antigens, lipoarabinomannan, phosphatidylinositol mannoside, and glucose monomycolate. Furthermore,...
We have characterized the CD1b-mediated presentation pathway for the mycobacterial lipoglycan lipoarabinomannan (LAM) in monocyte-derived antigen-presenting cells. The macrophage mannose receptor (MR) was responsible for uptake of LAM. Antagonism of MR function inhibited both the internalization of LAM and the presentation of this antigen to LAM-reactive T cells. Intracellular MRs were most abundant...
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