Abstract:
:The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have characterized NKT TCR recognition of CD1d molecules loaded with natural self-antigens (Ags) and report the 2.3 Å resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3β loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.
journal_name
Immunityjournal_title
Immunityauthors
Mallevaey T,Clarke AJ,Scott-Browne JP,Young MH,Roisman LC,Pellicci DG,Patel O,Vivian JP,Matsuda JL,McCluskey J,Godfrey DI,Marrack P,Rossjohn J,Gapin Ldoi
10.1016/j.immuni.2011.01.013subject
Has Abstractpub_date
2011-03-25 00:00:00pages
315-26issue
3eissn
1074-7613issn
1097-4180pii
S1074-7613(11)00034-3journal_volume
34pub_type
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