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Publication : Mouse and Human CD1d-Self-Lipid Complexes Are Recognized Differently by Murine Invariant Natural Killer T Cell Receptors.

First Author  Guo T Year  2016
Journal  PLoS One Volume  11
Issue  5 Pages  e0156114
PubMed ID  27213277 Mgi Jnum  J:253179
Mgi Id  MGI:6094798 Doi  10.1371/journal.pone.0156114
Citation  Guo T, et al. (2016) Mouse and Human CD1d-Self-Lipid Complexes Are Recognized Differently by Murine Invariant Natural Killer T Cell Receptors. PLoS One 11(5):e0156114
abstractText  Invariant natural killer T (iNKT) cells recognize self-lipids presented by CD1d through characteristic TCRs, which mainly consist of the invariant Valpha14-Jalpha18 TCRalpha chain and Vbeta8.2, 7 or 2 TCRbeta chains with hypervariable CDR3beta sequences in mice. The iNKT cell-CD1d axis is conserved between humans and mice, and human CD1d reactivity of murine iNKT cells have been described. However, the detailed differences between the recognition of human and mouse CD1d bound to various self-lipids by mouse iNKT TCRs are largely unknown. In this study, we generated a de novo murine iNKT TCR repertoire with a wider range of autoreactivity compared with that of naturally occurring peripheral iNKT TCRs. Vbeta8.2 mouse iNKT TCRs capable of recognizing the human CD1d-self-lipid tetramer were identified, although such clones were not detectable in the Vbeta7 or Vbeta2 iNKT TCR repertoire. In line with previously reports, clonotypic Vbeta8.2 iNKT TCRs with unique CDR3beta loops did not discriminate among lipids presented by mouse CD1d. Unexpectedly, however, these iNKT TCRs showed greater ligand selectivity toward human CD1d presenting the same lipids. Our findings demonstrated that the recognition of mouse and human CD1d-self-lipid complexes by murine iNKT TCRs is not conserved, thereby further elucidating the differences between cognate and cross-species reactivity of self-antigens by mouse iNKT TCRs.
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