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Recognition of a lipid antigen by CD1-restricted αβ+ T cells

Abstract

MAJOR histocompatibility complex (MHC) class I and class II molecules bind immunogenic peptides and present them to lymphocytes bearing the αβ T-cell antigen receptor (TCR)1–4. An analogous antigen-presenting function also has been proposed for the non-MHC-encoded CD1 molecules5, a family of non-polymorphic, β2-microglobulin-associated glycoproteins5–8 expressed on most professional antigen-presenting cells9–11. In support of this hypothesis, CD1 molecules are recognized by selected CD4CD8 αβ or γδ8TCR+ T-cell clones12–14, and we have recently shown that CD1 molecules restrict the recognition of foreign microbial antigens by αβTGR+ T cells10. But the substantial structural divergence of CD1 from MHC class I and class II molecules7, raises the possibility that the antigens presented by the CD1 system may differ fundamentally from those presented by MHC-encoded molecules. Here we report that a purified CDlb-restricted antigen of Mycobacterium tuberculosis presented to αβTCR+ T cells is mycolic acid, a family of α-branched, β-hydroxy, long-chain fatty acids found in mycobacteria15,16. This example of non-protein microbial antigen recognition suggests that αβTCR+ T cells recognize a broader range of antigens than previously appreciated and that at least one member of the CD1 family has evolved the ability to present lipid antigens.

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Beckman, E., Porcelli, S., Morita, C. et al. Recognition of a lipid antigen by CD1-restricted αβ+ T cells. Nature 372, 691–694 (1994). https://doi.org/10.1038/372691a0

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