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Structural and functional characterization of a novel T cell receptor co-regulatory protein complex, CD97-CD55.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2007 Jul 27; Vol. 282 (30), pp. 22023-32. Date of Electronic Publication: 2007 Apr 20. - Publication Year :
- 2007
-
Abstract
- CD97, the archetypal member of the EGF-TM7 protein family, is constitutively expressed on granulocytes and monocytes and rapidly up-regulated on T and B cells following activation. The key isoform of CD97 expressed on leukocytes binds the complement regulatory protein CD55 (also termed decay-accelerating factor). CD97 has been shown recently to mediate co-stimulation of T cells via CD55. Here, we demonstrate that blocking the interaction between CD55 on monocytes and CD97 on T cells leads to inhibition of proliferation and interferon-gamma secretion. This implies that bidirectional interactions between CD97 and CD55 are involved in T cell regulation. Structural studies presented here reveal the molecular basis for this activity. We have solved the structure of EMR2, a very close homolog of CD97, using x-ray crystallography. NMR-based chemical shift mapping of the EMR2-CD55 interaction has allowed us to generate a model for the CD97-CD55 complex. The structure of the complex reveals that the T cell and complement regulatory activities of CD55 occur on opposite faces of the molecule. This suggests that CD55 might simultaneously regulate both the innate and adaptive immune responses, and we have shown that CD55 can still regulate complement when bound to CD97.
- Subjects :
- Antigens, CD genetics
B-Lymphocytes immunology
CD55 Antigens genetics
Clone Cells
Crystallization
Cytokines analysis
Flow Cytometry
Genetic Variation
Humans
Leukocytes, Mononuclear immunology
Membrane Glycoproteins genetics
Receptors, G-Protein-Coupled
Antigens, CD physiology
CD55 Antigens physiology
Membrane Glycoproteins physiology
Receptors, Antigen, T-Cell physiology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 282
- Issue :
- 30
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17449467
- Full Text :
- https://doi.org/10.1074/jbc.M702588200