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

J Immunol. 2014 May 1;192(9):4054-60. doi: 10.4049/jimmunol.1400158. Epub 2014 Mar 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / immunology*
  • Antigens, CD1 / immunology
  • Base Sequence
  • Conserved Sequence / immunology
  • Flow Cytometry
  • Glycolipids / immunology
  • Humans
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / chemistry*
  • Receptors, Antigen, T-Cell / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / chemistry*
  • T-Lymphocyte Subsets / immunology

Substances

  • Antigens, CD1
  • CD1b antigen
  • Glycolipids
  • Receptors, Antigen, T-Cell