A molecular basis for NKT cell recognition of CD1d-self-antigen.

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

Immunity

journal_title

Immunity

authors

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 L

doi

10.1016/j.immuni.2011.01.013

subject

Has Abstract

pub_date

2011-03-25 00:00:00

pages

315-26

issue

3

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(11)00034-3

journal_volume

34

pub_type

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