Study of antigen-processing steps reveals preferences explaining differential biological outcomes of two HLA-A2-restricted immunodominant epitopes from human immunodeficiency virus type 1.
Cytotoxic T-lymphocyte (CTL) responses directed to different human immunodeficiency virus (HIV) epitopes vary in their protective efficacy. In particular, HIV-infected cells are much more sensitive to lysis by anti-Gag/p17(77-85)/HLA-A2 than to that by anti-polymerase/RT(476-484)/HLA-A2 CTL, because of a higher density of p17(77-85) complexes. This report describes multiple processing steps favoring the generation of p17(77-85) complexes: (i) the exact COOH-terminal cleavage of epitopes by cellular proteases occurred faster and more frequently for p17(77-85) than for RT(476-484), and (ii) the binding efficiency of the transporter associated with antigen processing was greater for p17(77-85) precursors than for the RT(476-484) epitope. Surprisingly, these peptides, which differed markedly in their antigenicity, displayed qualitatively and quantitatively similar immunogenicity, suggesting differences in the mechanisms governing these phenomena. Here, we discuss the mechanisms responsible for such differences.
Cohen
W M
WM
Institut National de la Santé et de la Recherche Médicale Unité 445, Institut Cochin de Génétique Moléculaire, Hôpital Cochin, 27 rue du faubourg Saint-Jacques, 75014 Paris, France. cohen@cochin.inserm.fr
Bianco
A
A
Connan
F
F
Camoin
L
L
Dalod
M
M
Lauvau
G
G
Ferriès
E
E
Culmann-Penciolelli
B
B
van Endert
P M
PM
Briand
J P
JP
Choppin
J
J
Guillet
J G
JG
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D001692:Biological Transport; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D015683:Gene Products, gag / Q000276:immunology* / Q000378:metabolism; D015488:HIV Antigens / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D054303:HIV Reverse Transcriptase / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D011498:Protein Precursors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015488:HIV Antigens; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D009097:Multienzyme Complexes; D011498:Protein Precursors; D011506:Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; C071313:LMP-2 protein; D054303:HIV Reverse Transcriptase; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex