Producing nature's gene-chips: The generation of peptides for display by MHC class I molecules

Nilabh Shastri, Susan Schwab, Thomas Serwold

Research output: Contribution to journalReview article

Abstract

Gene-chips contain thousands of nucleotide sequences that allow simultaneous analysis of the complex mixture of RNAs transcribed in cells. Like these gene-chips, major histocompatibility complex (MHC) class I molecules display a large array of peptides on the cell surface for probing by the CD8+ T cell repertoire. The peptide mixture represents fragments of most, if not all, intracellular proteins. The antigen processing machinery accomplishes the daunting task of sampling these proteins and cleaving them into the precise set of peptides displayed by MHC I molecules. It has long been believed that antigenic peptides arose as by-products of normal protein turnover. Recent evidence, however, suggests that the primary source of peptides is newly synthesized proteins that arise from conventional as well as cryptic translational reading frames. It is increasingly clear that for many peptides the C-terminus is generated in the cytoplasm, and N-terminal trimming occurs in the endoplasmic reticulum in an MHC I - dependent manner. Nature's gene-chips are thus both parsimonious and elegant.

Original languageEnglish (US)
Pages (from-to)463-493
Number of pages31
JournalAnnual Review of Immunology
Volume20
DOIs
StatePublished - Apr 20 2002
Externally publishedYes

Fingerprint

Oligonucleotide Array Sequence Analysis
Major Histocompatibility Complex
Peptides
Proteins
Reading Frames
Antigen Presentation
Complex Mixtures
Endoplasmic Reticulum
Cytoplasm
RNA
T-Lymphocytes

Keywords

  • Antigen presentation
  • Antigen processing
  • ER proteolysis
  • Proteasome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Producing nature's gene-chips : The generation of peptides for display by MHC class I molecules. / Shastri, Nilabh; Schwab, Susan; Serwold, Thomas.

In: Annual Review of Immunology, Vol. 20, 20.04.2002, p. 463-493.

Research output: Contribution to journalReview article

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N2 - Gene-chips contain thousands of nucleotide sequences that allow simultaneous analysis of the complex mixture of RNAs transcribed in cells. Like these gene-chips, major histocompatibility complex (MHC) class I molecules display a large array of peptides on the cell surface for probing by the CD8+ T cell repertoire. The peptide mixture represents fragments of most, if not all, intracellular proteins. The antigen processing machinery accomplishes the daunting task of sampling these proteins and cleaving them into the precise set of peptides displayed by MHC I molecules. It has long been believed that antigenic peptides arose as by-products of normal protein turnover. Recent evidence, however, suggests that the primary source of peptides is newly synthesized proteins that arise from conventional as well as cryptic translational reading frames. It is increasingly clear that for many peptides the C-terminus is generated in the cytoplasm, and N-terminal trimming occurs in the endoplasmic reticulum in an MHC I - dependent manner. Nature's gene-chips are thus both parsimonious and elegant.

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