Translating DRiPs: MHC class I immunosurveillance of pathogens and tumors

Abstract

MHC class I molecules display oligopeptides on the cell surface to enable T cell immunosurveillance of intracellular pathogens and tumors. Speed is of the essence in detecting viruses, which can complete a full replication cycle in just hours, whereas tumor detection is typically a finding-the-needle-in-the-haystack exercise. We review current evidence supporting a nonrandom, compartmentalized selection of peptidogenic substrates that focuses on rapidly degraded translation products as a main source of peptide precursors to optimize immunosurveillance of pathogens and tumors.

Keywords: antigen processing; compartmentalization; cotranslational degradation; nuclear translation; ribosome; translation.

Figure 1.. E Pluribus Unum: the many potential sources of antigenic peptides.

Dotted lines reflect newly proposed processes or cellular locations; these include the nuclear or cytosolic degradation of nuclear translation products, the contribution of immunoribosomes to DRiPs, the uncertainty about the requirement of the 19 S regulatory particle of the proteasome in DRiP generation, or the initial location of MHC class I/peptide clustering, which is experimentally detected, first in the Golgi Complex, but which likely occurs earlier in the secretory pathway. Noncanonical ORFs include nonannotated, small ORFs; uORFs; as well as ORFs using non-AUG start codons. QC, Quality control.