The T cell antigen receptor expressed by Valpha14i NKT cells has a unique mode of glycosphingolipid antigen recognition.
Natural killer (NK) 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 alpha-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 alpha-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 t(1/2). 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.
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
Stéphane
S
Sidobre
Kirsten J L
KJ
Hammond
Lise
L
Bénazet-Sidobre
Sergei D
SD
Maltsev
Stewart K
SK
Richardson
Rachel M
RM
Ndonye
Amy R
AR
Howell
Teruyuki
T
Sakai
Gurdyal S
GS
Besra
Steven A
SA
Porcelli
Mitchell
M
Kronenberg
D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000378:metabolism; D018949:Antigens, CD1 / Q000737:chemistry / Q000378:metabolism; D055610:Antigens, CD1d; D001665:Binding Sites; D016207:Cytokines / Q000096:biosynthesis; D006028:Glycosphingolipids / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D016207:Cytokines; D006028:Glycosphingolipids; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell