Human Mannose Receptor (CD206) in Immune Response
Human Mannose Receptor (CD206) in Immune Response
Evaluation of: He LZ, Crocker A, Lee J et al. Antigenic targeting of the human mannose receptor induces tumor immunity. J. Immunol. 178(10), 6259 - 6267 (2007).
Induction of adaptive immune response requires, in most cases, internalization of the antigen by professional antigen-presenting cells. Various endocytic receptors may mediate such interaction. However, little is known regarding the exact participation of such receptors in the context of immune response in vivo. This paper evaluates a recent work that utilizes one such molecule, the human CD206, transgenically incorporated into mouse, in order to establish its role in immune response. Such a study benefits from the fact that the function of the human form of the receptor is elaborated and thus would help to define new targets for future vaccine strategies.
Targeting endocytic receptors on professional antigen-presenting cells (APCs) for delivery of antigen(s) in order to enhance the antigen-specific immune response is gaining importance in current immunotherapy research. A recent study by He et al. has highlighted this approach by targeting with monoclonal antibodies (mAbs) one such endocytic receptor, the human macrophage mannose receptor or CD206 (hu CD206) transgenically incorporated in mice.
The fate of the APC-targeted antigen can be diverse: it can be either totally degraded or presented to responder T cells in order to induce either tolerogenicity or immunogenicity. The outcome depends on the type and state of activation of APCs. Recent studies in mice have clearly demonstrated the necessity of activation of APCs to obtain a sustained immune response when targeting dendritic cells (DCs) with mAbs specific for MHC class I or MHC class II pathways. However, other studies have pointed out that targeting with mAbs directed against MHC class II and CD11c molecules to stimulate humoral immune response does not require an activation signal in the form of an adjuvant. Thus, the issue of the adjuvant dependency, particularly in the case of humoral immune response, remains open for discussion.
The present study by He et al. elegantly explores this issue. The study illustrates that the induction of an immune response can be differentially manipulated by exploiting the role of an adjuvant. With the targeting mAb, a particular subclass of antibody response is efficiently mounted and is further enhanced by boosting, all in the absence of adjuvancy. With the high dose of the same targeting mAb, the authors show that antigen-specific proliferation of T cells is also induced in the absence of an adjuvant, an effect that is drastically reduced when a lower dose is used. However, such T-cell responses induced by even higher doses of mAb are not sustained beyond 4 - 5 days in the absence of an adjuvant. With the help of a tumor-eradication model, they further demonstrate that in order to induce a sustained effector T-cell differentiation, coadministration of an adjuvant is necessary.
The role of CD206 as a professional endocytic receptor in antigen presentation for inducing an immune response is controversial. Targeting CD206 either with mAb or mannosylated ligands has been shown to augment both class I and class II pathways of antigen presentation and T-cell response in in vitro studies. In an in vivo model using genetically deficient mice, CD206 was shown to be a catabolic receptor for serum glycoproteins without a significant role in protective immune response against a model infection. In addition, the presence of several other mannose-sensitive endocytic receptors on APC surface has denied CD206 its precise status in antigen presentation. The present study emphasizes the central issue of CD206-mediated immune response in a relevant in vivo system using human CD206 transgenically incorporated in mice. The study further provides an insight into the domain of targeted immune response and its possible use as a delivery system for a wide range of antigens to bring about beneficial immunological effect(s). Furthermore, the understanding of the immunological role of CD206 helps to determine its relevance in autoimmune and other pathological conditions.
Abstract and Introduction
Abstract
Evaluation of: He LZ, Crocker A, Lee J et al. Antigenic targeting of the human mannose receptor induces tumor immunity. J. Immunol. 178(10), 6259 - 6267 (2007).
Induction of adaptive immune response requires, in most cases, internalization of the antigen by professional antigen-presenting cells. Various endocytic receptors may mediate such interaction. However, little is known regarding the exact participation of such receptors in the context of immune response in vivo. This paper evaluates a recent work that utilizes one such molecule, the human CD206, transgenically incorporated into mouse, in order to establish its role in immune response. Such a study benefits from the fact that the function of the human form of the receptor is elaborated and thus would help to define new targets for future vaccine strategies.
Introduction
Targeting endocytic receptors on professional antigen-presenting cells (APCs) for delivery of antigen(s) in order to enhance the antigen-specific immune response is gaining importance in current immunotherapy research. A recent study by He et al. has highlighted this approach by targeting with monoclonal antibodies (mAbs) one such endocytic receptor, the human macrophage mannose receptor or CD206 (hu CD206) transgenically incorporated in mice.
The fate of the APC-targeted antigen can be diverse: it can be either totally degraded or presented to responder T cells in order to induce either tolerogenicity or immunogenicity. The outcome depends on the type and state of activation of APCs. Recent studies in mice have clearly demonstrated the necessity of activation of APCs to obtain a sustained immune response when targeting dendritic cells (DCs) with mAbs specific for MHC class I or MHC class II pathways. However, other studies have pointed out that targeting with mAbs directed against MHC class II and CD11c molecules to stimulate humoral immune response does not require an activation signal in the form of an adjuvant. Thus, the issue of the adjuvant dependency, particularly in the case of humoral immune response, remains open for discussion.
The present study by He et al. elegantly explores this issue. The study illustrates that the induction of an immune response can be differentially manipulated by exploiting the role of an adjuvant. With the targeting mAb, a particular subclass of antibody response is efficiently mounted and is further enhanced by boosting, all in the absence of adjuvancy. With the high dose of the same targeting mAb, the authors show that antigen-specific proliferation of T cells is also induced in the absence of an adjuvant, an effect that is drastically reduced when a lower dose is used. However, such T-cell responses induced by even higher doses of mAb are not sustained beyond 4 - 5 days in the absence of an adjuvant. With the help of a tumor-eradication model, they further demonstrate that in order to induce a sustained effector T-cell differentiation, coadministration of an adjuvant is necessary.
The role of CD206 as a professional endocytic receptor in antigen presentation for inducing an immune response is controversial. Targeting CD206 either with mAb or mannosylated ligands has been shown to augment both class I and class II pathways of antigen presentation and T-cell response in in vitro studies. In an in vivo model using genetically deficient mice, CD206 was shown to be a catabolic receptor for serum glycoproteins without a significant role in protective immune response against a model infection. In addition, the presence of several other mannose-sensitive endocytic receptors on APC surface has denied CD206 its precise status in antigen presentation. The present study emphasizes the central issue of CD206-mediated immune response in a relevant in vivo system using human CD206 transgenically incorporated in mice. The study further provides an insight into the domain of targeted immune response and its possible use as a delivery system for a wide range of antigens to bring about beneficial immunological effect(s). Furthermore, the understanding of the immunological role of CD206 helps to determine its relevance in autoimmune and other pathological conditions.