The molecular basis of CD1-mediated presentation of lipid antigens

D. Branch Moody, Gurdyal S. Besra, Ian A. Wilson, Steven A. Porcelli

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

The CD1 family of proteins mediates a newly described pathway for presentation of lipids and glycolipids for specific recognition by T cells. All four of the known human CD1 proteins (CD1a, CD1b, CD1c and CD1d) as well as murine CD1d have now been shown to mediate T-cell recognition of lipid or glycolipid antigens. These antigens include naturally occurring foreign glycolipids from intracellular pathogens or synthetic glycolipids that are related in structure to mammalian glycolipids. The CD1b and CD1d-presented antigens differ in their fine structures but reveal a general motif in which a rigid hydrophilic cap is bound to two aliphatic hydrocarbon chains. Different T-cell populations recognize individual antigens without cross-reactivity to closely related antigen structures or CD1 isoforms, documenting the complexity and fine specificity of CD1-mediated T-cell responses. Mapping of the molecular determinants of recognition for CD1b and CD1d-presented antigens reveals that T cells discriminate the fine structure of the hydrophilic cap of the antigen, but both the length and structure of the lipid chains may be altered without loss of recognition. This pattern of lipid antigen recognition may be accounted for by a simple molecular mechanism of presentation that parallels the known mechanism for presentation of peptides, but solves the special problems related to the hydrophobic chemical nature of the lipid antigens. We propose that CD1 binds antigen by accommodating the two lipid tails within the hydrophobic groove of its two membrane distal domains, positioning the rigid hydrophilic cap of the antigen on the solvent-exposed surface of the CD1 protein, where it can directly contact the T-cell antigen receptor. This model provides a molecular basis for recognition of a new and diverse set of T-cell antigens contained within the lipid bilayers of cellular membranes.

Original languageEnglish (US)
Pages (from-to)285-296
Number of pages12
JournalImmunological Reviews
Volume172
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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