TCR bias and affinity define two compartments of the CD1b–glycolipid-specific T cell repertoire

I Van Rhijn, NA Gherardin, A Kasmar… - The Journal of …, 2014 - journals.aai.org
I Van Rhijn, NA Gherardin, A Kasmar, W de Jager, DG Pellicci, L Kostenko, LL Tan, M Bhati…
The Journal of Immunology, 2014journals.aai.org
Current views emphasize TCR diversity as a key feature that differentiates the group 1
(CD1a, CD1b, CD1c) and group 2 (CD1d) CD1 systems. Whereas TCR sequence motifs
define CD1d-reactive NKT cells, the available data do not allow a TCR-based organization
of the group 1 CD1 repertoire. The observed TCR diversity might result from donor-to-donor
differences in TCR repertoire, as seen for MHC-restricted T cells. Alternatively, diversity
might result from differing CD1 isoforms, Ags, and methods used to identify TCRs. Using …
Abstract
Current views emphasize TCR diversity as a key feature that differentiates the group 1 (CD1a, CD1b, CD1c) and group 2 (CD1d) CD1 systems. Whereas TCR sequence motifs define CD1d-reactive NKT cells, the available data do not allow a TCR-based organization of the group 1 CD1 repertoire. The observed TCR diversity might result from donor-to-donor differences in TCR repertoire, as seen for MHC-restricted T cells. Alternatively, diversity might result from differing CD1 isoforms, Ags, and methods used to identify TCRs. Using CD1b tetramers to isolate clones recognizing the same glycolipid, we identified a previously unknown pattern of V gene usage (TRAV17, TRBV4-1) among unrelated human subjects. These TCRs are distinct from those present on NKT cells and germline-encoded mycolyl lipid–reactive T cells. Instead, they resemble the TCR of LDN5, one of the first known CD1b-reactive clones that was previously thought to illustrate the diversity of the TCR repertoire. Interdonor TCR conservation was observed in vitro and ex vivo, identifying LDN5-like T cells as a distinct T cell type. These data support TCR-based organization of the CD1b repertoire, which consists of at least two compartments that differ in TCR sequence motifs, affinity, and coreceptor expression.
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