Producing nature's gene-chips: the generation of peptides for display by MHC class I molecules.
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.
Shastri
Nilabh
N
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA. nshastri@socrates.berkeley.edu
Schwab
Susan
S
Serwold
Thomas
T
D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D018448:Models, Immunological; D009097:Multienzyme Complexes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019151:Peptide Library; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex
D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D019151:Peptide Library; D010455:Peptides; D010450:Endopeptidases; D000626:Aminopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex