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

Evan M. Beckman, Steven A. Porcelli, Craig T. Morita, Samuel M. Behar, Stephen T. Furlong, Michael B. Brenner

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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 GDI 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 CD4-CD8- αβ or γδ8TCR+ T-cell clones12-14, and we have recently shown that GDI molecules restrict the recognition of foreign microbial antigens by αβTGR+ T cells10. But the substantial structural divergence of GDI from MHC class I and class II molecules7, raises the possibility that the antigens presented by the GDI 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 GDI family has evolved the ability to present lipid antigens.

Original languageEnglish (US)
Pages (from-to)691-694
Number of pages4
JournalNature
Volume372
Issue number6507
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

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    Beckman, E. M., Porcelli, S. A., Morita, C. T., Behar, S. M., Furlong, S. T., & Brenner, M. B. (1994). Recognition of a lipid antigen by GDI-restricted αβ+ T cells. Nature, 372(6507), 691-694. https://doi.org/10.1038/372691a0