Presentation of newly synthesized glycoproteins to CD4+ T lymphocytes. An analysis using influenza hemagglutinin transport mutants.
Human lymphoblastoid cells transiently expressing the hemagglutinin (HA) glycoprotein of influenza virus are rapidly and efficiently recognized by CD4+ HA-specific T lymphocytes. This endogenous presentation pathway is sensitive to chloroquine and is therefore likely related to the classical class II major histocompatibility complex (MHC) exogenous pathway of antigen presentation. In this study we have examined a series of transport-defective HA mutants. We correlate the intracellular fate of the native antigen with its presentation characteristics. We have found that the native antigen must enter the secretory pathway since a cytosolic form is not presented. However, surface expression and normal trafficking through the Golgi apparatus are not required for efficient presentation. Instead, escape of native antigen from the endoplasmic reticulum appears to be both necessary and sufficient for gaining access to a compartment where antigen is processed and binds class II MHC molecules.
Kittlesen
D J
DJ
Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville 22908.
Brown
L R
LR
Braciale
V L
VL
Sambrook
J P
JP
Gething
M J
MJ
Braciale
T J
TJ
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D001692:Biological Transport / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D004247:DNA; D005434:Flow Cytometry; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D004247:DNA