TY - JOUR
T1 - The T cell antigen receptor expressed by Valpha14iNKT cells has a unique mode of glycosphingolipid antigen recognition
AU - Sidobre, S
AU - Hammond, KJ
AU - Benazet-Sidobre, L
AU - Malstev, SD
AU - Richardson, SK
AU - Ndonye, RM
AU - Besra, Gurdyal
PY - 2004/8/10
Y1 - 2004/8/10
N2 - Natural killer (INK) T cells with an invariant Valpha14 rearrangement (Valpha14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid CL-galactosyl ceramide (alpha-GalCer) presented by CD1d, and they may have important regulatory functions. It was previously shown that the Valpha14i T cell antigen receptor (TCR) has a high affinity for the alpha-GalCer/CD1d complex, driven by a long half-life (t(1/2)). Although this result could have reflected the unique attributes of a-GalCer, using several related glycolipid compounds, we show here that the threshold for full activation of Valpha14i NKT cells by these glycosphingolipids requires a relatively high-affinity TCR interaction with a long t1/2. Furthermore, our data are consistent with the view that the mechanism of recognition of these compounds presented by CD1d to the Valpha14i NKT cell TCR is likely to fit a lock-and-key model. Overall, these findings emphasize the distinct properties of glycosphingolipid antigen recognition by Valpha14i NKT cells.
AB - Natural killer (INK) T cells with an invariant Valpha14 rearrangement (Valpha14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid CL-galactosyl ceramide (alpha-GalCer) presented by CD1d, and they may have important regulatory functions. It was previously shown that the Valpha14i T cell antigen receptor (TCR) has a high affinity for the alpha-GalCer/CD1d complex, driven by a long half-life (t(1/2)). Although this result could have reflected the unique attributes of a-GalCer, using several related glycolipid compounds, we show here that the threshold for full activation of Valpha14i NKT cells by these glycosphingolipids requires a relatively high-affinity TCR interaction with a long t1/2. Furthermore, our data are consistent with the view that the mechanism of recognition of these compounds presented by CD1d to the Valpha14i NKT cell TCR is likely to fit a lock-and-key model. Overall, these findings emphasize the distinct properties of glycosphingolipid antigen recognition by Valpha14i NKT cells.
UR - http://www.scopus.com/inward/record.url?scp=4344651706&partnerID=8YFLogxK
U2 - 10.1073/pnas.0404632101
DO - 10.1073/pnas.0404632101
M3 - Article
C2 - 15304644
SN - 1091-6490
VL - 101
SP - 12254
EP - 12259
JO - National Academy of Sciences. Proceedings
JF - National Academy of Sciences. Proceedings
ER -