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.
Sidobre
Stéphane
S
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
Hammond
Kirsten J L
KJ
Bénazet-Sidobre
Lise
L
Maltsev
Sergei D
SD
Richardson
Stewart K
SK
Ndonye
Rachel M
RM
Howell
Amy R
AR
Sakai
Teruyuki
T
Besra
Gurdyal S
GS
Porcelli
Steven A
SA
Kronenberg
Mitchell
M
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