Non-CD28 Costimulatory Molecules Present in T Cell Rafts Induce T Cell Costimulation by Enhancing the Association of TCR with Rafts

• Published in: The Journal of immunology (1950) 2000-02, Vol.164 (3), p.1251-1259
• Main Authors: Yashiro-Ohtani, Yumi, Zhou, Xu-Yu, Toyo-oka, Kazuhito, Tai, Xu-Guang, Park, Cheung-Seog, Hamaoka, Toshiyuki, Abe, Ryo, Miyake, Kensuke, Fujiwara, Hiromi
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - physiology; Animals; Antibodies, Monoclonal - metabolism; Antigens, CD - immunology; Antigens, CD - metabolism; beta-Cyclodextrins; Calcium - metabolism; CD2 antigen; CD28 antigen; CD28 Antigens - physiology; CD3 antigen; CD3 Complex - immunology; CD3 Complex - metabolism; CD44 antigen; CD48 Antigen; CD5 antigen; CD5 Antigens - immunology; CD5 Antigens - metabolism; CD9 antigen; Cell Fractionation; Cyclodextrins - pharmacology; Detergents; Glycolipids - immunology; Glycolipids - metabolism; Ligands; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Receptors, Antigen, T-Cell - metabolism; Receptors, Antigen, T-Cell - physiology; Signal Transduction - drug effects; Signal Transduction - immunology; Solubility; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thy-1 Antigens - immunology; Thy-1 Antigens - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.3.1251

While CD28 functions as the major T cell costimulatory receptor, a number of other T cell molecules have also been described to induce T cell costimulation. Here, we investigated the mechanisms by which costimulatory molecules other than CD28 contribute to T cell activation. Non-CD28 costimulatory molecules such as CD5, CD9, CD2, and CD44 were present in the detergent-insoluble glycolipid-enriched (DIG) fraction/raft of the T cell surface, which is rich in TCR signaling molecules and generates a TCR signal upon recruitment of the TCR complex. Compared with CD3 ligation, coligation of CD3 and CD5 as an example of DIG-resident costimulatory molecules led to an enhanced association of CD3 and DIG. Such a DIG redistribution markedly up-regulated TCR signaling as observed by ZAP-70/LAT activation and Ca2+ influx. Disruption of DIG structure using an agent capable of altering cholesterol organization potently diminished Ca2+ mobilization induced by the coligation of CD3 and CD5. This was associated with the inhibition of the redistribution of DIG although the association of CD3 and CD5 was not affected. Thus, the DIG-resident costimulatory molecules exert their costimulatory effects by contributing to an enhanced association of TCR/CD3 and DIG.