title: The segment of invariant chain that is critical for association with major histocompatibility complex class II molecules contains the sequence of a peptide eluted from class II polypeptides.
abstract: Major histocompatibility complex class II molecules present peptides from an extracellular source of antigens to CD4+ T lymphocytes. The class II-associated invariant chain affects this role of alpha and beta polypeptides by restriction of peptide loading to endocytic vesicles. Up to now no specific portion of the invariant chain has been defined as the class II binding site. We constructed recombinant invariant chain genes and inspected association of the mutant invariant chains with class II polypeptides. Here we demonstrate that an extracytoplasmic sequence of the invariant chain (aa 81-109) that is only 23 residues away from the transmembrane region is essential for contact with class II polypeptides, whereas the remaining C-terminal part is dispensable for binding. The sequence of invariant-chain-derived peptides that were eluted from class II molecules is contained in this segment and may define the class II binding site of the invariant chain. The membrane-proximal position of this region suggests that the invariant chain and invariant-chain-derived peptides isolated from class II molecules bind to a domain distinct from the class II pocket.
authors.affiliation: Section of Immunobiology, University of Bonn, Germany.
authors.forename: I M
authors.initials: IM
authors.lastname: Freisewinkel
authors.forename: K
authors.initials: K
authors.lastname: Schenck
authors.forename: N
authors.initials: N
authors.lastname: Koch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; C045084:invariant chain