title: CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation.
abstract: CD2 is an intercellular adhesion molecule that has been implicated in T cell activation and differentiation both in humans and mice. Although the ligand for human CD2 has been defined as LFA-3, that for murine CD2 has not been identified yet. To identify the ligand for mouse CD2, we generated a chimeric molecule consisting of the extracellular domain of mouse CD2 and human immunoglobulin (Ig)G1 Fc (mCD2Rg). A hamster monoclonal antibody (mAb), HM48-1, was established by screening mAbs that could block the binding of mCD2Rg to T cell lines at the ligand site. The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein with an apparent molecular mass of 45 kD, which were shared characteristics with human LFA-3. However, its expression was predominantly restricted to hematopoietic cells, unlike human LFA-3. Protein microsequencing analysis for the NH2-terminal 18 amino acid residues of the affinity-purified HM48-1 antigen revealed that it is almost identical with mouse CD48. This identity was further confirmed by the reactivity of HM48-1 with a soluble recombinant CD48 (sCD48) protein and the molecule recognized by a rat mAb raised against sCD48. A rat anti-CD48 mAb blocked the mCD2Rg binding as well as HM48-1. Moreover, sCD48 also inhibited the mCD2Rg binding to the cellular ligand. Finally, like anti-CD2 mAb, HM48-1 inhibited the phytohemagglutinin response and, when crosslinked, augmented the anti-CD3 response of splenic T cells. These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Koyanagi
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Takanashi
authors.forename: Y W
authors.initials: YW
authors.lastname: Wong
authors.forename: A F
authors.initials: AF
authors.lastname: Williams
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: H
authors.initials: H
authors.lastname: Yagita
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D001483:Base Sequence; D018801:CD2 Antigens; D000071178:CD48 Antigen; D018968:CD58 Antigens; D006224:Cricetinae; D008024:Ligands; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D018968:CD58 Antigens; C000604066:Cd48 protein, mouse; C000604067:Cd48 protein, rat; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins