Another view of T cell antigen recognition: cooperative engagement of glycolipid antigens by Va14Ja18 natural T(iNKT) cell receptor [corrected].
Va14Ja18 natural T (iNKT) cells rapidly elicit a robust effector response to different glycolipid Ags, with distinct functional outcomes. Biochemical parameters controlling iNKT cell function are partly defined. However, the impact of iNKT cell receptor beta-chain repertoire and how alpha-galactosylceramide (alpha-GalCer) analogues induce distinct functional responses have remained elusive. Using altered glycolipid ligands, we discovered that the Vb repertoire of iNKT cells impacts recognition and Ag avidity, and that stimulation with suboptimal avidity Ag results in preferential expansion of high-affinity iNKT cells. iNKT cell proliferation and cytokine secretion, which correlate with iNKT cell receptor down-regulation, are induced within narrow biochemical thresholds. Multimers of CD1d1-alphaGalCer- and alphaGalCer analogue-loaded complexes demonstrate cooperative engagement of the Va14Ja18 iNKT cell receptor whose structure and/or organization appear distinct from conventional alphabeta TCR. Our findings demonstrate that iNKT cell functions are controlled by affinity thresholds for glycolipid Ags and reveal a novel property of their Ag receptor apparatus that may have an important role in iNKT cell activation.
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Aleksandar K
AK
Stanic
R
R
Shashidharamurthy
Jelena S
JS
Bezbradica
Naoto
N
Matsuki
Yoshitaka
Y
Yoshimura
Sachiko
S
Miyake
Eun Young
EY
Choi
Todd D
TD
Schell
Luc
L
Van Kaer
Satvir S
SS
Tevethia
Derry C
DC
Roopenian
Takashi
T
Yamamura
Sebastian
S
Joyce
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D002460:Cell Line; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D005699:Galactosylceramides / Q000276:immunology* / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013110:Sphingosine / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013110:Sphingosine