TY - JOUR
T1 - Vβ2 natural killer T cell antigen receptor-mediated recognition of CD1d-glycolipid antigen
AU - Patel, Onisha
AU - Pellicci, Daniel G.
AU - Uldrich, Adam P.
AU - Sullivan, Lucy C.
AU - Bhati, Mugdha
AU - McKnight, Melissa
AU - Richardson, Stewart K.
AU - Howell, Amy R.
AU - Mallevaey, Thierry
AU - Zhang, Jingjing
AU - Bedel, Romain
AU - Besra, Gurdyal S.
AU - Brooks, Andrew G.
AU - Kjer-Nielsen, Lars
AU - McCluskey, James
AU - Porcelli, Steven A.
AU - Gapin, Laurent
AU - Rossjohn, Jamie
AU - Godfrey, Dale I.
PY - 2011/11/22
Y1 - 2011/11/22
N2 - Natural killer T cell antigen receptors (NKT TCRs) recognize lipidbased antigens (Ags) presented by CD1d. Although the TCR α-chain is invariant, NKT TCR Vβ exhibits greater diversity, with one (Vβ11) and three (Vβ8, Vβ7, and Vβ2) Vβ chains in humans and mice, respectively. With the exception of the Vβ2 NKT TCR, NKT TCRs possess canonical tyrosine residues within complementarity determining region (CDR) 2β that are critical for CD1d binding. Thus, how Vβ2 NKT TCR docks with CD1d-Ag was unclear. Despite the absence of the CDR2β-encoded tyrosine residues, we show that the Vβ2 NKT TCR engaged CD1d-Ag in a similar manner and with a comparable affinity and energetic footprint to the manner observed for the Vβ8.2 and Vβ7 NKT TCRs. Accordingly, the germline-encoded regions of the TCR β-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 Vβ2 NKT TCR and the Vβ8.2 and Vβ7 NKT TCRs, with the Vβ2 NKT TCR exhibiting greater sensitivity to modifications to the glycolipid Ag. Furthermore, within the Vβ2 NKT TCR-CD1d-αGalCer complex, the CDR2β loop mediated fewer contacts with CD1d, whereas the CDR1β and CDR3β loops contacted CD1d to a much greater extent compared with most Vβ11, Vβ8.2, and Vβ7 NKT TCRs. Accordingly, there is a greater interplay between the germline- and nongermline-encoded loops within the TCR β-chain of the Vβ2 NKT TCR that enables CD1d-Ag ligation.
AB - Natural killer T cell antigen receptors (NKT TCRs) recognize lipidbased antigens (Ags) presented by CD1d. Although the TCR α-chain is invariant, NKT TCR Vβ exhibits greater diversity, with one (Vβ11) and three (Vβ8, Vβ7, and Vβ2) Vβ chains in humans and mice, respectively. With the exception of the Vβ2 NKT TCR, NKT TCRs possess canonical tyrosine residues within complementarity determining region (CDR) 2β that are critical for CD1d binding. Thus, how Vβ2 NKT TCR docks with CD1d-Ag was unclear. Despite the absence of the CDR2β-encoded tyrosine residues, we show that the Vβ2 NKT TCR engaged CD1d-Ag in a similar manner and with a comparable affinity and energetic footprint to the manner observed for the Vβ8.2 and Vβ7 NKT TCRs. Accordingly, the germline-encoded regions of the TCR β-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 Vβ2 NKT TCR and the Vβ8.2 and Vβ7 NKT TCRs, with the Vβ2 NKT TCR exhibiting greater sensitivity to modifications to the glycolipid Ag. Furthermore, within the Vβ2 NKT TCR-CD1d-αGalCer complex, the CDR2β loop mediated fewer contacts with CD1d, whereas the CDR1β and CDR3β loops contacted CD1d to a much greater extent compared with most Vβ11, Vβ8.2, and Vβ7 NKT TCRs. Accordingly, there is a greater interplay between the germline- and nongermline-encoded loops within the TCR β-chain of the Vβ2 NKT TCR that enables CD1d-Ag ligation.
KW - Conserved docking
KW - T cell repertoire
UR - http://www.scopus.com/inward/record.url?scp=82755187762&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82755187762&partnerID=8YFLogxK
U2 - 10.1073/pnas.1109066108
DO - 10.1073/pnas.1109066108
M3 - Article
C2 - 22065767
AN - SCOPUS:82755187762
SN - 0027-8424
VL - 108
SP - 19007
EP - 19012
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 47
ER -