Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2

• Published in: Nature (London) 2002-10, Vol.419 (6907), p.629-633
• Main Authors: Kumanogoh, Atsushi, Marukawa, Satoko, Suzuki, Kazuhiro, Takegahara, Noriko, Watanabe, Chie, Ch'ng, EweSeng, Ishida, Isao, Fujimura, Harutoshi, Sakoda, Saburo, Yoshida, Kanji, Kikutani, Hitoshi
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Analysis of the immune response. Humoral and cellular immunity; Animals; Antigens, CD; Antigens, Differentiation, T-Lymphocyte - immunology; B-Lymphocytes - immunology; Biological and medical sciences; Cell interactions; CHO Cells; Cloning; Cloning, Molecular; Cricetinae; Dendritic Cells - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humanities and Social Sciences; Humans; Immunobiology; letter; Lymphocyte Activation; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Membrane Proteins - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; multidisciplinary; Peptides; Polymorphism, Genetic; Proteins; Rats; Receptors, Antigen, T-Cell - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; Rodents; Science; Science (multidisciplinary); Semaphorins; T-Lymphocytes - immunology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature01037

Semaphorins are a family of phylogenetically conserved soluble and transmembrane proteins 1 , 2 . Although many soluble semaphorins deliver guidance cues to migrating axons during neuronal development 3 , 4 , 5 , some members are involved in immune responses 6 , 7 , 8 , 9 . For example, CD100 (also known as Sema4D), a class IV transmembrane semaphorin, signals through CD72 to effect nonredundant roles in immune responses 7 , 10 , 11 , 12 , 13 in a ligand–receptor system that is distinct from any seen previously in the nervous system 14 , 15 . Here we report that the class IV semaphorin Sema4A, which is expressed in dendritic cells and B cells, enhances the in vitro activation and differentiation of T cells and the in vivo generation of antigen-specific T cells. Treating mice with monoclonal antibodies against Sema4A blocks the development of an experimental autoimmune encephalomyelitis that is induced by an antigenic peptide derived from myelin oligodendrocyte glycoprotein. In addition, expression cloning shows that the Sema4A receptor is Tim-2, a member of the family of T-cell immunoglobulin domain and mucin domain (Tim) proteins that is expressed on activated T cells.