TY - JOUR
T1 - V beta 2 natural killer T cell antigen receptor-mediated recognition of CD1d-glycolipid antigen
AU - Patel, O
AU - Pellicci, DG
AU - Uldrich, AP
AU - Sullivan, LC
AU - Bhati, M
AU - McKnight, M
AU - Richardson, SK
AU - Howell, AR
AU - Mallevaey, T
AU - Zhang, J
AU - Bedel, R
AU - Besra, Gurdyal
AU - Brooks, AG
AU - Kjer-Nielsen, L
AU - McCluskey, J
AU - Porcelli, SA
AU - Gapin, L
AU - Rossjohn, J
AU - Godfrey, DI
PY - 2011/11/1
Y1 - 2011/11/1
N2 - Natural killer T cell antigen receptors (NKT TCRs) recognize lipid-based antigens (Ags) presented by CD1d. Although the TCR alpha-chain is invariant, NKT TCR V beta exhibits greater diversity, with one (V beta 11) and three (V beta 8, V beta 7, and V beta 2) V beta chains in humans and mice, respectively. With the exception of the V beta 2 NKT TCR, NKT TCRs possess canonical tyrosine residues within complementarity determining region (CDR) 2 beta that are critical for CD1d binding. Thus, how V beta 2 NKT TCR docks with CD1d-Ag was unclear. Despite the absence of the CDR2 beta-encoded tyrosine residues, we show that the V beta 2 NKT TCR engaged CD1d-Ag in a similar manner and with a comparable affinity and energetic footprint to the manner observed for the V beta 8.2 and V beta 7 NKT TCRs. Accordingly, the germline-encoded regions of the TCR beta-chain do not exclusively dictate the innate NKT TCR-CD1d-Ag docking mode. Nevertheless, clear fine specificity differences for the CD1d-Ag existed between the V beta 2 NKT TCR and the V beta 8.2 and V beta 7 NKT TCRs, with the V beta 2 NKT TCR exhibiting greater sensitivity to modifications to the glycolipid Ag. Furthermore, within the V beta 2 NKT TCR-CD1d-alpha GalCer complex, the CDR2 beta loop mediated fewer contacts with CD1d, whereas the CDR1 beta and CDR3 beta loops contacted CD1d to a much greater extent compared with most V beta 11, V beta 8.2, and V beta 7 NKT TCRs. Accordingly, there is a greater interplay between the germline-and nongermline-encoded loops within the TCR beta-chain of the V beta 2 NKT TCR that enables CD1d-Ag ligation.
AB - Natural killer T cell antigen receptors (NKT TCRs) recognize lipid-based antigens (Ags) presented by CD1d. Although the TCR alpha-chain is invariant, NKT TCR V beta exhibits greater diversity, with one (V beta 11) and three (V beta 8, V beta 7, and V beta 2) V beta chains in humans and mice, respectively. With the exception of the V beta 2 NKT TCR, NKT TCRs possess canonical tyrosine residues within complementarity determining region (CDR) 2 beta that are critical for CD1d binding. Thus, how V beta 2 NKT TCR docks with CD1d-Ag was unclear. Despite the absence of the CDR2 beta-encoded tyrosine residues, we show that the V beta 2 NKT TCR engaged CD1d-Ag in a similar manner and with a comparable affinity and energetic footprint to the manner observed for the V beta 8.2 and V beta 7 NKT TCRs. Accordingly, the germline-encoded regions of the TCR beta-chain do not exclusively dictate the innate NKT TCR-CD1d-Ag docking mode. Nevertheless, clear fine specificity differences for the CD1d-Ag existed between the V beta 2 NKT TCR and the V beta 8.2 and V beta 7 NKT TCRs, with the V beta 2 NKT TCR exhibiting greater sensitivity to modifications to the glycolipid Ag. Furthermore, within the V beta 2 NKT TCR-CD1d-alpha GalCer complex, the CDR2 beta loop mediated fewer contacts with CD1d, whereas the CDR1 beta and CDR3 beta loops contacted CD1d to a much greater extent compared with most V beta 11, V beta 8.2, and V beta 7 NKT TCRs. Accordingly, there is a greater interplay between the germline-and nongermline-encoded loops within the TCR beta-chain of the V beta 2 NKT TCR that enables CD1d-Ag ligation.
KW - T cell repertoire
KW - conserved docking
U2 - 10.1073/pnas.1109066108
DO - 10.1073/pnas.1109066108
M3 - Article
C2 - 22065767
SN - 1091-6490
VL - 108
SP - 19007
EP - 19012
JO - National Academy of Sciences. Proceedings
JF - National Academy of Sciences. Proceedings
IS - 47
ER -