抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

B and T lymphocytes are the mediators of immunity, but their function is under the control of dendritic cells. Dendritic cells in the periphery capture and process antigens, express lymphocyte co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses. They not only activate lymphocytes, they also tolerize T cells to antigens that are innate to the body (self-antigens), thereby minimizing autoimmune reactions. Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis. With knowledge comes the realization that these cells are a powerful tool for manipulating the immune system.

Dendritic cells and the control of immunity

Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.

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The blockade of immune checkpoints in cancer immunotherapy

Comprehensive Integration of Single-Cell Data.

Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.

Immunobiology of Dendritic Cells

Inhibitory MHC class I receptors on NK and T cells: a standard nomenclature

2B4-mediated activation of human natural killer cells.

Human and rodent CD200 are recognized by the inhibitory CD200R, and these molecules play an important role in the regulation of the immune system. Several viruses, such as human herpesvirus-6 (HHV-6), HHV-7, and HHV-8, possess a CD200 homologue, suggesting that these viruses regulate the immune response via CD200R. In this study, we analyzed the effect of human CD200 and the viral CD200 homologues on human CD200R-expressing cells. We found that human CD200R is predominantly expressed on basophils in amounts higher than on other human peripheral blood leukocytes. Furthermore, the viral CD200 homologues as well as human CD200 were recognized by human CD200R, and the activation of basophils was down-regulated by these CD200 proteins. These results suggested that CD200R is an important regulatory molecule of basophil activation. In addition, the presence of CD200 homologues on several viruses suggests a potentially unique relationship between basophil function and viral infection.

Down-Regulation of Basophil Function by Human CD200 and Human Herpesvirus-8 CD200

Karre and colleagues observed that tumors lacking H-2 molecules were more susceptible to NK cell-mediated lysis than tumors expressing class I and proposed a unique mechanism of immune surveillance for ‘missing self’ (1). The molecular mechanism responsible for this phenomenon has been defined by the identification of membrane receptors on NK cells that bind to MHC class I on potential target cells. While the NK cell receptors initiating a cell-mediated response against tumors or virus-infected cells are not yet understood, killing of certain target cells can be partially or totally inhibited if the cells express MHC class I molecules that engage inhibitory receptors on the NK cell. Surprisingly, four distinct types of NK cell receptors for MHC class I that inhibit NK cell-mediated cytotoxicity have been identified.

Activating and Inhibitory NK Cell Receptors

DNAX accessory molecule-1 (DNAM-1) is a signal-transducing adhesion molecule involved in the cytolytic function mediated by CTL and NK cells. In the present study, we have investigated various perimeters of DNAM-1-mediated signaling and adhesion. Although adhesion of DNAM-1 to its ligand does not require divalent cations, protein synthesis, or RNA transcription, activation of protein kinase C (PKC) is required for DNAM-1 functioning. Furthermore, mutation of the putative PKC-binding site in the cytoplasmic domain of DNAM-1 (Ser329 to Phe329) prevents both ligand binding and PMA-induced phosphorylation of the DNAM-1 receptor. These results indicate that PKC phosphorylates Ser329 of DNAM-1 and plays a critical role for both DNAM-1 adhesion and signaling.

Lewis L. Lanier

Papers

Inhibitory MHC class I receptors on NK and T cells: a standard nomenclature

2B4-mediated activation of human natural killer cells.

Down-Regulation of Basophil Function by Human CD200 and Human Herpesvirus-8 CD200

Activating and Inhibitory NK Cell Receptors

Protein kinase C is involved in the regulation of both signaling and adhesion mediated by DNAX accessory molecule-1 receptor