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The liver is a tolerogenic organ with exquisite mechanisms of immune regulation that ensure upkeep of local and systemic immune tolerance to self and foreign antigens, but that is also able to mount effective immune responses against pathogens. The immune privilege of liver allografts was recognized first in pigs in spite of major histo-compatibility complex mismatch, and termed the ＂liver tolerance effect＂. Furthermore, liver transplants are spontaneously accepted with only low-dose immunosuppression, and induce tolerance for non-hepatic co-transplanted allografts of the same donor. Although this immunotolerogenic environment is favorable in the setting of organ transplantation, it is detrimental in chronic infectious liver diseases like hepatitis B or C, malaria, schistosomiasis or tumorigenesis, leading to pathogen persistence and weak anti-tumor effects. The liver is a primary site of T-cell activation, but it elicits poor or incomplete activation of T cells, leading to their abortive activation, exhaustion, suppression of their effector function and early death. This is exploited by pathogens and can impair pathogen control and clearance or allow tumor growth. Hepatic priming of T cells is mediated by a number of local conventional and nonconventional antigen-presenting cells （APCs）, which promote tolerance by immune deviation, induction of T-cell anergy or apoptosis, and generating and expanding regulatory T cells. This review will focus on the communication between classical and nonclassical APCs and lymphocytes in the liver in tolerance induction and will discuss recent insights into the role of innate lymphocytes in this process.

Objective： This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin （β2M）, a conservative immune molecule in vertebrate.Data Sources： The data used in this review were obtained from PubMed up to October 2015.Terms of β2M, immune response, and infection were used in the search.Study Selections： Articles related to β2M were retrieved and reviewed.Articles focusing on the characteristic and function of β2M were selected.The exclusion criteria of articles were that the studies on β2M-related molecules.Results： β2M is critical for the immune surveillance and modulation in vertebrate animals.The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases.β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies.It also involves in forming major histocompatibility complex （MHC class Ⅰ or MHC Ⅰ） or like heterodimers, covering from antigen presentation to immune homeostasis.Conclusions： Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools.Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.

The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex （MHC） molecules at the cell surface. Interaction between peptide-MHC （pMHC） and the T cell receptor （TCR） is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR ＇signatures＇ raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome.

The uterus in early pregnancy is a non-lymphoid organ that is enriched in natural killer （NK） cells. Studies to address the role of these abundant human NK cells at the maternal/fetal interface have focused on their response to the major histocompatibility complex （MHC） molecules on fetal trophoblast cells that they contact. The interaction of maternal NK cell receptors belonging to the killer cell immunoglobulin-like receptor （KIR） family with trophoblast MHC class I molecules in pregnancy can regulate NK cell activation for secretion of pro-angiogenic factors that promote placental development. This review will cover the role of KIR at the maternal/fetal interface and focus on KIR2DL4, a KIR family member that is uniquely poised to play a role in pregnancy due to the restricted expression of its ligand, human leukocyte antigen （HLA）-G, by fetal trophoblast cells early in pregnancy. The pathways by which KIR2DL4-HLA-G interactions induce the cellular senescence of NK cells and the role of the resulting senescence-associated secretory phenotype （SASP） in vascular remodeling will be discussed in the context of reproduction.

Attenuated Listeria monocytogenes （LM） is a promising candidate vector for the delivery of cancer vaccines. After phagocytosis by antigen-presenting cells, this bacterium stimulates the major histocompatibility complex （MHC）-I and MHC-II pathways and induces the proliferation of antigen-specific T lymphocytes. A new strategy involving genetic modification of the replication-deficient LM strain AdalAdat （Lmdd） to express and secrete human CD24 protein has been developed. CD24 is a hepatic cancer stem cell biomarker that is closely associated with apoptosis, metastasis and recurrence of hepatocellular carcinoma （HCC）. After intravenous administration in mice, Lmdd-CD24 was distributed primarily in the spleen and liver and did not cause severe organ injury. Lmdd-CD24 effectively increased the number of interferon （IFN）-7-producing CD8＋ T cells and IFN-7 secretion. Lmdd-CD24 also enhanced the number of IL-4- and IL-lO-producing T helper 2 cells. The efficacy of the Lmdd-CD24 vaccine was further investigated against Hepa1- 6-CD24 tumors, which were inguinally inoculated into mice. Lmdd-CD24 significantly reduced the tumor size in mice and increased their survival. Notably, a reduction of T regulatory cell （Treg） numbers and an enhancement of specific CD8＋ T-cell activity were observed in the tumor-infiltrating lymphocytes （TILs）. These results suggest a potential application of the Lmdd-CD24 vaccine against HCC.

The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator （HVEM/BTLA） signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper （Tfh） cells （B220-, CD4＋ CXCR5＋ PD-lhigh）, extrafollicular helper cells （B220-, CD4＋ CXCR5- PD-1＋ and PD-1-） and germinal centre （GC） B cells （B220＋Fas＋ GL7＋） were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.

HLA-A＊02 is the most prevalent and polymorphic major histocompatibility complex （MHC） allele family in humans. Functional differences have been revealed among subtypes, demanding further subtyping of HLA-A＊02 in basic and clinical settings. However, the fast growing polymorphisms render traditional primeror probe-based typing methods impractical and result in increasing ambiguities in direct sequence-based typing. In this study, we combined group-specific amplification and mono-allelic sequencing to design and validate a simple scheme for the complete screening and accurate subtyping of all 540 reported HLA-A＊02 alleles. This scheme could be performed in routine labs to facilitate studies with an interest in HLA-A＊02.

In the last two decades, it has become clear that yo T cells recognize a diverse array of antigens including self and foreign, large and small, and peptidic and non-peptidic molecules. In this respect, 78 antigens as a whole resemble more the antigens recognized by antibodies than those recognized by T cells. Because of this antigenic diversity, no single mechanism--such as the major histocompatibility complex （MHC） restriction of ap T cells--is likely to provide a basis for all observed T-cell antigen receptor （TCR）-dependent 78 T-cell responses. Furthermore, available evidence suggests that many individual 78 T cells are poly-specific, probably using different modes of ligand recognition in their responses to unrelated antigens. While posing a unique challenge in the maintenance of self-tolerance, this broad reactivity pattern might enable multiple overlapping uses of 78 T-cell populations, and thus generate a more efficient immune response.

To date, molecular regulation of dendritic cell （DC） differentiation and DC-mediated immune deviation has been incompletely understood. DCs, which have long been recog- nized as highly potent antigen-presenting cells, play critical roles in linking innate immune functions with adaptive immunity. DCs belong to the hematopoietic system and arise from CD34＋ stem cells in the bone marrow. After taking up antigenic materials, DCs process and present them to their membrane surface in the form of major histocompatibility complex （MHC） class I/or class II molecule-antigen peptide complexes,

The proteasome is a large, polymeric protease complex responsible for the degradation of intracellular pro- teins and generation of peptides that bind to class I major histocompatibility complex （MHC） molecules. This study identified a new member of proteasomal subunits in turbots （Scophthalrnus rnaxirnus）. The full- length cDNA sequence of turbot proteasomal subunit was obtained. Sequence analysis indicated that its primary structure is highly similar to that of LMP7 from other vertebrates. The relationship between the turbot LMP7 expression and immune responses to pathogen infection was reported. Quantitative reverse transcriptase polymerase chain reaction showed that LMPTwas expressed differently in various tissues, with higher expression in the spleen, liver, muscle, and skin. The LMP7 expression was the highest at 96 h after challenge with lymphocyctis disease virus （LCDV） and at 12 h after challenge with Vibrio anguillarurn in the turbot liver, kidney, and spleen. Furthermore, the LMP7 expression distinctly increased in turbot kidney cells at 24 h after challenge with V. anguillarurn and at 96 h after challenge with LCDV. These results indicate that the turbot LMP7 protein participates in immune responses and may play a significant role in the immune process.