Editors' ChoiceImmunology

Making Oneself Presentable

Science's STKE  01 Jun 2004:
Vol. 2004, Issue 235, pp. tw196-TW196
DOI: 10.1126/stke.2352004TW196

Once activated, cytotoxic CD8+ T cells react to changes in the protein content of a cell that take place when the cell becomes virally infected or transformed. Degraded protein fragments, which are generated by the proteasome, associate with major histocompatibility complex class I proteins within the endoplasmic reticulum and traffic to the cell surface to be scanned by responsive T cells. However, in order to prime a naïve T cell, the first encounter with peptide must be accompanied by an array of activation signals, which are generally only provided by professional antigen-presenting cells (APCs). The APCs must somehow acquire peptides without themselves being infected or transformed (see the Perspective by Ploegh). Studies by Wolkers et al. and Norbury et al. show that this process, which is known as cross-priming, depends critically on the location of the peptide within its parent protein. Peptides derived from regions proximal to, or within, the signal sequence were profoundly inefficient at stimulating T cells when compared with more distal peptides--presumably because signal sequences are degraded most quickly and are present at very low levels in the cell. A critical parameter in determining cross-presentation efficiency is the acquisition of intact proteins or peptides, rather than their proteasome-generated products, by the APC.

H. L. Ploegh, Nothing 'gainst time's scythe can make defense... Science 304, 1262-1263 (2004). [Summary] [Full Text]

C. C. Norbury, S. Basta, K. B. Donohue, D. C. Tscharke, M. F. Princiotta, P. Berglund, J. Gibbs, J. R. Bennink, J. W. Yewdell, CD8+ T cell cross-priming via transfer of proteasome substrates. Science 304, 1318-1321 (2004). [Abstract] [Full Text]

M. C. Wolkers, N. Brouwenstijn, A. H. Bakker, M. Toebes, T. N. M. Schumacher, Antigen bias in T cell cross-priming. Science 304, 1314-1317 (2004). [Abstract] [Full Text]