Rethinking peptide supply to MHC class I molecules.
The notion that peptides bound to MHC class I molecules are derived mainly from newly synthesized proteins that are defective, and are therefore targeted for immediate degradation, has gained wide acceptance. This model, still entirely hypothetical, has strong intuitive appeal and is consistent with some experimental results, but it is strained by other findings, as well as by established and emerging concepts in protein quality control. While not discounting defectiveness as a driving force for the processing of some proteins, we propose that MHC-class-I-restricted epitopes are derived mainly from nascent proteins that are accessed by the degradation machinery prior to any assessment of fitness, and we outline one way in which this could be accomplished.
Eisenlohr
Laurence C
LC
Laurence C. Eisenlohr, Lan Huang and Tania N. Golovina are at the Thomas Jefferson University, Jefferson Medical College, Department of Microbiology and Immunology, Philadelphia, Philadelphia 19107, USA.
Huang
Lan
L
Golovina
Tania N
TN
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D010455:Peptides