Strictly transporter of antigen presentation (TAP)-dependent presentation of an immunodominant cytotoxic T lymphocyte epitope in the signal sequence of a virus protein.
Peptides presented by major histocompatibility complex (MHC) class I molecules are derived from intracellularly synthesized proteins. Cytosolic proteins are fragmented into peptides, which are subsequently transported via the transporter of antigen presentation (TAP) into the endoplasmic reticulum (ER), where they bind to MHC class I molecules. We have investigated the requirements for MHC class I presentation of the immunodominant gp33 cytotoxic T lymphocyte epitope of the lymphocytic choriomeningitis virus. This epitope is located within the leader peptide of the virus glycoprotein. Such an epitope is expected to be presented in a TAP-independent manner, since it is released into the ER by signal peptidase. Taking advantage of TAP1-/- mice, however, we show both in vitro and in vivo that, after virus infection, the presentation of the gp33 epitope is strictly dependent on a functional TAP heterodimer. The results are discussed with respect to peptide trimming processes in the ER.
Hombach
J
J
Department of Pathology, University of Zürich, Switzerland.
Pircher
H
H
Tonegawa
S
S
Zinkernagel
R M
RM
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D021382:Protein Sorting Signals / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins
D000956:Antigens, Viral; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D006183:H-2 Antigens; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus