Lipids in T Cell Presentation

Science's STKE  27 Jan 2004:
Vol. 2004, Issue 217, pp. tw35-TW35
DOI: 10.1126/stke.2172004TW35

Immune detection by T cells can involve the recognition of specific lipids (see the Perspective by De Libero), as well as protein-derived antigens. Unlike the well-characterized intracellular pathways that load and present peptides, scant detail has been available about how lipid antigens come to be processed and presented. Zhou et al. find that members of a family of proteins known to transfer lipids during synthesis and degradation within the endosome also assist in extracting and loading lipids onto CD1d molecules, which present the lipids to T cells. In the absence of such lipid-transfer protein genes, mice failed to present particular lipids and displayed defects in development of a major subset of CD1d-specific T cells. Moody et al. describe a new species of naturally occurring ligands presented by CD1a with an unusual antigenic structure in which peptides are chemically complexed with lipid. These lipopeptides resemble essential iron-scavenging siderophores from mycobacteria. Thus, CD1-based microbial immune detection may have evolved to recognize molecular species specifically generated during obligate survival pathways of bacteria.

G. De Libero, The Robin Hood of antigen presentation. Science 303, 485-487 (2004). [Summary] [Full Text]

D. Zhou, C. Cantu III, Y. Sagiv, N. Schrantz, A. B. Kulkarni, X. Qi, D. J. Mahuran, C. R. Morales, G. A. Grabowski, K. Benlagha, P. Savage, A. Bendelac, L. Teyton, Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins. Science 303, 523-527 (2004). [Abstract] [Full Text]

D. B. Moody, D. C. Young, T.-Y. Cheng, J.-P. Rosat, C. Roura-mir, P. B. O'Connor, D. M. Zajonc, A. Walz, M. J. Miller, S. B. Levery, I. A. Wilson, C. E. Costello, M. B. Brenner, T cell activation by lipopeptide antigens. Science 303, 527-531 (2004). [Abstract] [Full Text]