CD1a-autoreactive T cells are a normal component of the human αβ T cell repertoire

Nat Immunol. 2010 Dec;11(12):1102-9. doi: 10.1038/ni.1956. Epub 2010 Oct 31.

Abstract

CD1 activates T cells, but the function and size of the possible human T cell repertoires that recognize each of the CD1 antigen-presenting molecules remain unknown. Using an experimental system that bypasses major histocompatibility complex (MHC) restriction and the requirement for defined antigens, we show that polyclonal T cells responded at higher rates to cells expressing CD1a than to those expressing CD1b, CD1c or CD1d. Unlike the repertoire of invariant natural killer T (NKT) cells, the CD1a-autoreactive repertoire contained diverse T cell antigen receptors (TCRs). Functionally, many CD1a-autoreactive T cells homed to skin, where they produced interleukin 22 (IL-22) in response to CD1a on Langerhans cells. The strong and frequent responses among genetically diverse donors define CD1a-autoreactive cells as a normal part of the human T cell repertoire and CD1a as a target of the T(H)22 subset of helper T cells.

Publication types

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

MeSH terms

  • Antigens, CD1 / immunology*
  • Autoimmunity / immunology*
  • Cell Separation
  • Chemotaxis, Leukocyte / immunology
  • Enzyme-Linked Immunospot Assay
  • Flow Cytometry
  • Humans
  • Interleukins / immunology
  • Interleukins / metabolism
  • Langerhans Cells / immunology
  • Langerhans Cells / metabolism
  • Lymphocyte Activation / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / cytology
  • Skin / immunology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • Antigens, CD1
  • CD1a antigen
  • Interleukins
  • Receptors, Antigen, T-Cell, alpha-beta
  • interleukin-22