The CD1 system: Antigen-presenting molecules for T cell recognition of lipids and glycolipids

Steven A. Porcelli, Robert L. Modlin

Research output: Contribution to journalReview article

584 Scopus citations

Abstract

Recent studies have identified the CD1 family of proteins as novel antigen-presenting molecules encoded by genes located outside of the major histocompatibility complex. CD1 proteins are conserved in all mammalian species so far examined and are prominently expressed on cells involved in antigen presentation, which suggests a role in activation of cell-mediated immunity. This has now been confirmed by functional studies demonstrating the ability of CD1 proteins to restrict the antigen-specific responses oft cells in humans and mice. Identification of naturally occurring antigens presented by CD1 has revealed the surprising finding that these are predominantly a variety of foreign lipids and glycolipids, including several found prominently in the cell walls and membranes of pathogenic mycobacteria. Structural, biochemical, and biophysical studies support the view that CD1 proteins bind the hydrophobic alkyl portions of these antigens directly and position the polar or hydrophilic head groups of bound lipids and glycolipids for highly specific interactions with T cell antigen receptors. Presentation of antigens by CD1 proteins requires uptake and intracellular processing by antigen presenting cells, and evidence exists for cellular pathways leading to the presentation of both exogenous and endogenous lipid antigens. T cells recognizing antigens presented by CD1 have a range of functional activities that suggest they are likely to mediate an important component of antimicrobial immunity and may also contribute to autoimmunity and host responses against neoplastic cells.

Original languageEnglish (US)
Pages (from-to)297-329
Number of pages33
JournalAnnual Review of Immunology
Volume17
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Cell-mediated immunity
  • Glycolipid antigens
  • Microbial immunity
  • Nonpeptide antigens
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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