UNSPECIFIED. (2004) Discriminating self from nonself with short peptides from large proteomes. IMMUNOGENETICS, 56 (5). pp. 311-319. ISSN 0093-7711

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Abstract

We studied whether the peptides of nine amino acids (9-mers) that are typically used in MHC class I presentation are sufficiently unique for self:nonself discrimination. The human proteome contains 28,783 proteins, comprising 10(7) distinct 9-mers. Enumerating distinct 9-mers for a variety of microorganisms we found that the average overlap, i.show $132#e., the probability that a foreign peptide also occurs in the human self, is about 0.2%. This self:nonself overlap increased when shorter peptides were used, e.show $132#g., was 30% for 6-mers and 3% for 7-mers. Predicting all 9-mers that are expected to be cleaved by the immunoproteasome and to be translocated by TAP, we find that about 25% of the self and the nonself 9-mers are processed successfully. For the HLA-A*0201 and HLA-A*0204 alleles, we predicted which of the processed 9-mers from each proteome are expected to be presented on the MHC. Both alleles prefer to present processed 9-mers to nonprocessed 9-mers, and both have small preference to present foreign peptides. Because a number of amino acids from each 9-mer bind the MHC, and are therefore not exposed to the TCR, antigen presentation seems to involve a significant loss of information. Our results show that this is not the case because the HLA molecules are fairly specific. Removing the two anchor residues from each presented peptide, we find that the self:nonself overlap of these exposed 7-mers resembles that of 9-mers. Summarizing, the 9-mers used in MHC class I presentation tend to carry sufficient information to detect nonself peptides amongst self peptides.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology > QR180 Immunology
Journal or Publication Title:	IMMUNOGENETICS
Publisher:	SPRINGER
ISSN:	0093-7711
Date:	August 2004
Volume:	56
Number:	5
Number of Pages:	9
Page Range:	pp. 311-319
Identification Number:	10.1007/s00251-004-0691-0
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/8116

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