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-Galactosylceramide: Low Affinity, Low Specificity for CD1d, High Affinity for 
TCRs1
* Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037;
Department of Pathology, University of Chicago, Chicago, IL 60637; and
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84601
CD1 resembles both class I and class II MHC but differs by the important aspect of presenting lipid/glycolipids, instead of peptides, to T cells. Biophysical studies of lipid/CD1 interactions have been limited, and kinetics of binding are in contradiction with functional studies. We have revisited this issue by designing new assays to examine the loading of CD1 with lipids. As expected for hydrophobic interactions, binding affinity was not high and had limited specificity. Lipid critical micelle concentration set the limitation to these studies. Once loaded onto CD1d, the recognition of glycolipids by 
T cell receptor was studied by surface plasmon resonance using soluble V14-V8.2 T cell receptors. The V14 J18 chain could be paired with NK1.1 cell-derived V chain, or any V8 chain, to achieve high affinity recognition of -galactosylceramide. Biophysical analysis indicated little effect of temperature or ionic strength on the binding interaction, in contrast to what has been seen in peptide/MHC-TCR studies. This suggests that there is less accommodation made by this TCR in recognizing -galactosylceramide, and it can be assumed that the most rigid part of the Ag, the sugar moiety, is critical in the interaction.
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