Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments

Ya Hui Chiu, Jayanthi Jayawardena, Angela Weiss, Daniel Lee, Se-Ho Park, Alice Dautry-Varsat, Albert Bendelac

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

Although recent studies have indicated that the major histocompatibility complex-like, β2-microglobulin-associated CD1 molecules might function to present a novel chemical class of antigens, lipids and glycolipids, to α/β T cells, little is known about the T cell subsets that interact with CD1. A subset of CD1d-autoreactive, natural killer (NK)1.1 receptor-expressing α/β T cells has recently been identified. These cells, which include both CD4 - CD8 - and CD4 + T cells, preferentially use an invariant Vα14-Jα281 T cell receptor (TCR) α chain paired with a Vβ8 TCR β chain in mice, or the homologous Vα24-JαQ/Vβ11 in humans. This cell subset can explosively release key cytokines such as interleukin (IL)-4 and interferon (IFN)-γ upon TCR engagement and may regulate a variety of infectious and autoimmune conditions. Here, we report the existence of a second subset of CD1d- restricted CD4 + T cells that do not express the NK1.1 receptor or the Vα14 TCR. Like the Vα14 + NK1.1 + T cells, these T cells exhibit a high frequency of autoreactivity to CD1d, use a restricted albeit distinct set of TCR gene families, and contribute to the early burst of IL-4 and IFN-γ induced by intravenous injection of anti-CD3. However, the Vα14 + NK1.1 + and Vα14 - NK1.1 - T cells differ markedly in their requirements for self-antigen presentation. Antigen presentation to the Vα14 + NK1.1 + cells requires endosomal targeting of CD1d through a tail-encoded tyrosine-based motif, whereas antigen presentation to the Vα14 - NK1.1 - cells does not. These experiments suggest the existence of two phenotypically different subsets of CD1d-restricted T cells that survey self-antigens loaded in distinct cellular compartments.

Original languageEnglish
Pages (from-to)103-110
Number of pages8
JournalJournal of Experimental Medicine
Volume189
Issue number1
DOIs
Publication statusPublished - 1999 Jan 4
Externally publishedYes

Fingerprint

Autoantigens
T-Cell Antigen Receptor
T-Lymphocytes
Antigen Presentation
Interleukin-4
Interferons
T-Cell Receptor Genes
Glycolipids
T-Lymphocyte Subsets
Major Histocompatibility Complex
Intravenous Injections
Tyrosine
Tail
Cytokines
Lipids
Antigens

Keywords

  • CD1
  • Endosome
  • Interferon γ
  • Interleukin 4
  • Self-antigen

ASJC Scopus subject areas

  • Immunology

Cite this

Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments. / Chiu, Ya Hui; Jayawardena, Jayanthi; Weiss, Angela; Lee, Daniel; Park, Se-Ho; Dautry-Varsat, Alice; Bendelac, Albert.

In: Journal of Experimental Medicine, Vol. 189, No. 1, 04.01.1999, p. 103-110.

Research output: Contribution to journalArticle

Chiu, Ya Hui ; Jayawardena, Jayanthi ; Weiss, Angela ; Lee, Daniel ; Park, Se-Ho ; Dautry-Varsat, Alice ; Bendelac, Albert. / Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments. In: Journal of Experimental Medicine. 1999 ; Vol. 189, No. 1. pp. 103-110.
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