Generation of MHC class I peptide antigens by protein processing in the secretory route by furin.
Cytosolic degradation of endogenously synthesized proteins by the proteasome and translocation of processed peptides to the endoplasmic reticulum by the transporters associated with antigen presentation constitutes the classical route for antigen presentation by MHC class I proteins. We have previously defined an alternative pathway in the secretory route involving proteolytic maturation of precursor proproteins for chimeric hepatitis B virus secretory core protein HBe containing a class I epitope at its carboxy-terminus. We extend those results by demonstrating that intracellular delivery of the trans-Golgi network protease furin increases both proteolytic maturation and antigen presentation of the chimeric HBe proteins. An additional class I epitope from the HIV envelope gp160 protein was inserted into this COOH-terminal region of two different chimeric HBe proteins. This epitope was also presented to CTL in a transporter-independent manner involving furin, and protein maturation and antigen presentation were also enhanced by furin over-expression. Presentation of this second epitope was restricted by a different class I allele, thus suggesting that antigen presentation by this new pathway may apply to any antigenic epitope and class I molecule. These results define the furin proteolytic maturation pathway of HBe in the secretory route as a general antigen processing route for MHC class I presentation.
Gil-Torregrosa
B C
BC
Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, 28220 Madrid, Spain.
Castaño
A R
AR
López
D
D
Del Val
M
M
D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D012634:Bodily Secretions / Q000502:physiology*; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D045683:Furin; D006513:Hepatitis B e Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013381:Subtilisins / Q000378:metabolism*
D000941:Antigens; D000939:Epitopes; D006513:Hepatitis B e Antigens; D010455:Peptides; D011993:Recombinant Fusion Proteins; D013381:Subtilisins; D045683:Furin