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Publication Highlights 2016

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A characteristic of mucosal-associated invariant T (MAIT) cells is the expression of TRAV1-2+ T cell receptors (TCRs) that are activated by riboflavin metabolite-based antigens (Ag) presented by the MHC-I related molecule, MR1. Whether the MR1-restricted T cell repertoire and associated Ag responsiveness extends beyond these cells remains unclear. Here, we describe MR1 autoreactivity and folate-derivative reactivity in a discrete subset of TRAV1-2+ MAIT cells. This recognition was attributable to CDR3β loop-mediated effects within a consensus TRAV1-2+ TCR-MR1-Ag footprint. Furthermore, we have demonstrated differential folate- and riboflavin-derivative reactivity by a diverse population of “atypical” TRAV1-2− MR1-restricted T cells. We have shown that TRAV1-2− T cells are phenotypically heterogeneous and largely distinct from TRAV1-2+ MAIT cells. A TRAV1-2− TCR docks more centrally on MR1, thereby adopting a markedly different molecular footprint to the TRAV1-2+ TCR. Accordingly, diversity within the MR1-restricted T cell repertoire leads to differing MR1-restricted Ag specificity.

Immunity. Jan 2016
 

 

 

Molecular mimicry between the 9B2 and 9C1 TCR-CD1d-[alpha]-GalCer complexes.

 

Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d–a-galactosylceramide (a-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1 þ type I NKT cell repertoire. These cells express a range of TCR a- and b-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7–8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A0 -pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with a-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d–a-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.

Nature Communications Feb 2016