Analyzing the Number of Antigenic Peptides

Science's STKE  09 Sep 2003:
Vol. 2003, Issue 199, pp. tw355-TW355
DOI: 10.1126/stke.2003.199.tw355

The major histocompatibility complex class I restricted T cells must react to abnormalities in the protein expression of a cell arising from cellular transformation, or infection with viruses and intracellular bacteria, but leave normal cells alone. The extent of this surveillance is the subject of two reports (see the Perspective by Yewdell). Using a bicistronic transgene construct, Schwab et al. initiated translation within a designated "untranslated" region of a gene starting with a nonstandard CUG codon. The peptide derived from this cryptic translation product was presented to the immune system with relatively high efficiency, inducing both immune tolerance and CD8 responses in different settings. Thus, through novel modes of translation, the realm of self or nonself presented to the immune system may extend well beyond that made available by the coding region of a given gene. Viruses frequently avoid host detection by limiting the amount of viral antigen they produce. In the case of the Epstein Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1), antigen limitation is thought to be achieved through inhibition of protein degradation by a glycine-alanine repeat (GAr) within the protein. However, such a mechanism would not be effective against nonGAr-containing defective ribosomal products (DriPs), nonfunctional polypeptides that are thought to represent a significant source of antigens. In revisiting this question, Yin et al. show that GAr also auto-inhibits EBNA1 translation, and thus limits both full-length protein and DRiP translation.

J. W. Yewdell, Hide and seek in the peptidome. Science 301, 1334-1335 (2003). [Summary] [Full Text]

S. R. Schwab, K. C. Li, C. Kang, N. Shastri, Constitutive display of cryptic translation products by MHC class I molecules. Science 301, 1367-1371 (2003). [Abstract] [Full Text]

Y. Yin, B. Manoury, R. Fåhraeus, Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1. Science 301, 1371-1374 (2003). [Abstract] [Full Text]