title: Invariant chain targets HLA class II molecules to acidic endosomes containing internalized influenza virus.
abstract: The role of the HLA class II-associated invariant chain in the intracellular trafficking of HLA-DR molecules was examined in a transient expression system using HeLa cells. In the absence of alpha and beta polypeptides, invariant chain was retained in the endoplasmic reticulum (ER). In the absence of invariant chain, intracellular alpha beta heterodimers could be detected only in the ER and the Golgi apparatus. However, when alpha and beta subunits were coexpressed with invariant chain, HLA-DR molecules were detectable in peripheral cytoplasmic vesicles, which also contained invariant chain. In addition, an antibody directed to an acid-induced conformational determinant on the influenza hemagglutinin molecule detected internalized influenza virus in the HLA-DR-containing vesicles. These findings provide direct evidence that the invariant chain targets class II molecules to an acidic endosomal compartment and that this compartment, long suspected to be the site of antigen processing, is the site where class II molecules interact with natural antigen.
authors.affiliation: Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: C A
authors.initials: CA
authors.lastname: Lamb
authors.forename: J W
authors.initials: JW
authors.lastname: Yewdell
authors.forename: J R
authors.initials: JR
authors.lastname: Bennink
authors.forename: P
authors.initials: P
authors.lastname: Cresswell
mesh_terms: D000906:Antibodies; D004721:Endoplasmic Reticulum / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology; D046911:Macromolecular Substances; D010957:Plasmids; D011995:Recombination, Genetic; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D000906:Antibodies; D006684:HLA-DR Antigens; D046911:Macromolecular Substances