Human membrane cofactor protein (MCP, CD46): multiple isoforms and functions

Seya, Tsukasa; Hirano, Akiko; Matsumoto, Misako; Nomura, Midori; Ueda, Shigeharu

doi:10.1016/s1357-2725(99)00092-8

Cited by 74 publications

(58 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To prevent nonspecific C3b degradation, for instance in the case of proper complement activation, Factor I requires cofactors for its proteolytic activity. These cofactors include membrane cofactor protein (MCP; CD46), complement receptor 1 (CR1), and Factor H which are either intrinsic membrane proteins on host cells or have various mechanisms to ensure preferential cofactor activity on host surfaces, and thereby limit complement activation in these contexts and prevent bystander tissue damage [38][39][40].…”

Section: Regulation Of Complement Activationmentioning

confidence: 99%

Complement and its role in innate and adaptive immune responses

2009

View full text Add to dashboard Cite

The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.

show abstract

Section: Regulation Of Complement Activationmentioning

confidence: 99%

Complement and its role in innate and adaptive immune responses

2009

View full text Add to dashboard Cite

show abstract

“…CD46 (previously called Membrane Cofactor Protein, MCP) is a ubiquitously expressed protein, first identified as a member of the regulators of complement activation family (Seya et al, 1999). It is a type I membrane protein which is a regulatory part of the complement system.…”

Section: -Cd46 T Cell Activation and Il-10 Production 3a Cd46mentioning

confidence: 99%

Abnormal Tr1 differentiation in multiple sclerosis

Astier¹,

Hafler²

2007

Journal of Neuroimmunology

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). In the recent years, accumulating evidence has supported an immunosuppressive role for regulatory T cells (Tregs). Most studies in the context of autoimmunity have focused on the defects of the CD4 + CD25 high Tregs. However, we recently demonstrated an altered function of Tr1 Treg cells in MS, characterized by a lack of IL-10 secretion. Therefore, several major regulatory T cell defects are involved in human autoimmune disease. Hence, the induction of Tregs or the stimulation of Treg activity may be beneficial for the treatment of such diseases.

show abstract

“…CD46 is a member of a family of glycoproteins called regulators of complement activation (RCA); these proteins serve to protect autologous host cells from complement-mediated lysis (reviewed in 7,8). The human genome encodes at least 6 RCA glycoproteins, some membrane-associated and others fluidphase.…”

Section: Human Herpesvirus 6 (Hhv-6)mentioning

confidence: 99%

“…For each pathogen whose CD46-interacting regions have been defined, the determinants are distinct from (although overlapping with) those involved in normal ligand binding and cofactor function, i.e. CD46 SCRs 2-4 are involved in binding of both C3b and C4b; SCR1 also influences C4b binding (7,8,15,35,43).…”

Section: Cd46 Domains Required For Hhv-6 Receptor Functionmentioning

confidence: 99%

Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor Function

Greenstone

Santoro²,

Lusso³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

We employed a quantitative cell fusion assay to identify structural domains of CD46 required for its function as a receptor for human herpesvirus 6 (HHV-6). We examined the activities of recombinant variants of CD46, including different isoforms as well as engineered truncations and molecular chimeras with decay-accelerating factor, a related protein in the family of regulators of complement activation (RCA). We observed strong receptor activity for all four CD46 isoforms, which differ in the membrane-proximal extracellular and cytoplasmic domains, indicating that the critical determinants for HHV-6 receptor activity reside outside the C-terminal portion of CD46. Analysis of the short consensus repeat (SCR) regions that comprise most of the extracellular portion of CD46 indicated a strong dependence on SCRs 2 and 3 and no requirement for SCRs 1 or 4. Fusion-inhibition studies with SCR-specific monoclonal antibodies supported the essential role of SCRs 2 and 3 in HHV-6 receptor activity. These findings contrast markedly with fusion mediated by measles virus glycoproteins for which we observed a strict dependence on SCRs 1 and 2, consistent with previous reports. These results expand the emerging notion that CD46 and other members of the RCA family are co-opted in distinct manners by different infectious pathogens.

show abstract

Human membrane cofactor protein (MCP, CD46): multiple isoforms and functions

Cited by 74 publications

References 16 publications

Complement and its role in innate and adaptive immune responses

Complement and its role in innate and adaptive immune responses

Abnormal Tr1 differentiation in multiple sclerosis

Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor Function

Contact Info

Product

Resources

About