Vbeta2 natural killer T cell antigen receptor-mediated recognition of CD1d-glycolipid antigen

Onisha G Patel, Daniel G Pellicci, Adam P Uldrich, Lucy C Sullivan, Mugdha Bhati, Melissa A McKnight, Stewart K Richardson, Amy R Howell, Thierry Mallevaey, JingJing Zhang, Romain Bedel, Gurdyal Besra, Andrew G Brooks, Lars Kjer-Nielsen, James McCluskey, Steven A Porcelli, Laurent Gapin, Jamie Rossjohn, Dale I Godfrey

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34 Citations (Scopus)

Abstract

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 Vbeta exhibits greater diversity, with one (Vbeta11) and three (Vbeta8, Vbeta7, and Vbeta2) Vbeta chains in humans and mice, respectively. With the exception of the Vbeta2 NKT TCR, NKT TCRs possess canonical tyrosine residues within complementarity determining region (CDR) 2beta that are critical for CD1d binding. Thus, how Vbeta2 NKT TCR docks with CD1d-Ag was unclear. Despite the absence of the CDR2beta-encoded tyrosine residues, we show that the Vbeta2 NKT TCR engaged CD1d-Ag in a similar manner and with a comparable affinity and energetic footprint to the manner observed for the Vbeta8.2 and Vbeta7 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 Vbeta2 NKT TCR and the Vbeta8.2 and Vbeta7 NKT TCRs, with the Vbeta2 NKT TCR exhibiting greater sensitivity to modifications to the glycolipid Ag. Furthermore, within the Vbeta2 NKT TCR-CD1d-alphaGalCer complex, the CDR2beta loop mediated fewer contacts with CD1d, whereas the CDR1beta and CDR3beta loops contacted CD1d to a much greater extent compared with most Vbeta11, Vbeta8.2, and Vbeta7 NKT TCRs. Accordingly, there is a greater interplay between the germline- and nongermline-encoded loops within the TCR beta-chain of the Vbeta2 NKT TCR that enables CD1d-Ag ligation.
Original languageEnglish
Pages (from-to)19007 - 19012
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number47
DOIs
Publication statusPublished - 2011

Cite this

Patel, O. G., Pellicci, D. G., Uldrich, A. P., Sullivan, L. C., Bhati, M., McKnight, M. A., Richardson, S. K., Howell, A. R., Mallevaey, T., Zhang, J., Bedel, R., Besra, G., Brooks, A. G., Kjer-Nielsen, L., McCluskey, J., Porcelli, S. A., Gapin, L., Rossjohn, J., & Godfrey, D. I. (2011). Vbeta2 natural killer T cell antigen receptor-mediated recognition of CD1d-glycolipid antigen. Proceedings of the National Academy of Sciences of the United States of America, 108(47), 19007 - 19012. https://doi.org/10.1073/pnas.1109066108