title: CD96 interaction with CD155 via its first Ig-like domain is modulated by alternative splicing or mutations in distal Ig-like domains.
abstract: The adhesion receptor CD96 (TACTILE) is a transmembrane glycoprotein possessing three extracellular immunoglobulin-like domains. Among peripheral blood cells, CD96 is expressed on T cells as well as NK cells and a subpopulation of B cells. A possible function of this receptor in NK cell-mediated killing activities was suggested recently. Moreover, CD96 was described as a tumor marker for T-cell acute lymphoblastic leukemia and acute myeloid leukemia. CD96 binds to CD155 (poliovirus receptor) and nectin-1, an adhesion receptor related to CD155. Here we report that human but not mouse CD96 is expressed in two splice variants possessing either an I-like (variant 1) or V-like (variant 2) second domain. With the notable exception of an AML tumor sample, variant 2 predominates in all the CD96-expressing cell types and tissues examined. Using chimeric human/murine CD96 receptors, we show that the interaction with its ligands is mediated via the outermost V-like domain. In contrast to mouse, however, the binding of human CD96 to CD155 is sensitive to the characteristics of the two downstream domains. This is illustrated by a significantly weaker CD96/CD155 interaction mediated by variant 1 when compared with variant 2. Moreover, recent evidence suggested that mutations in human CD96 correlate with the occurrence of a rare form of trigonocephaly. One such mutation causing a single amino acid exchange in the third domain of human CD96 decreased the capacity of both variants to bind to CD155 considerably, suggesting that a CD96-driven adhesion to CD155 may be crucial in developmental processes.
authors.affiliation: Institute of Immunology, Department of Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Meyer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Seth
authors.forename: Jana
authors.initials: J
authors.lastname: Albrecht
authors.forename: Michael K
authors.initials: MK
authors.lastname: Maier
authors.forename: Louis
authors.initials: L
authors.lastname: du Pasquier
authors.forename: Inga
authors.initials: I
authors.lastname: Ravens
authors.forename: Lutz
authors.initials: L
authors.lastname: Dreyer
authors.forename: Renate
authors.initials: R
authors.lastname: Burger
authors.forename: Martin
authors.initials: M
authors.lastname: Gramatzki
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schwinzer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Reinhold
authors.initials: R
authors.lastname: Foerster
authors.forename: Günter
authors.initials: G
authors.lastname: Bernhardt
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017510:Protein Folding; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D015703:Antigens, CD; C116131:CD96 antigen; D007136:Immunoglobulins; D008024:Ligands; D011991:Receptors, Virus; C066100:poliovirus receptor