The myelodysplastic syndromes (MDS) comprises a heterogeneous group of clonal hematopoietic stem cell disorders, while immunological abnormalities are frequently observed in such patients. T-cell mediated suppression of hematopoietic precursors contributes to the cytopenia and is related to the initiation and development of myelodysplastic syndromes (MDS). In this review, current knowledge concerning the feature of T-cell clonal expansion in MDS based on the analysis of T-cell receptor repertoire is summarized, including following issues: autoimmunity in MDS patients associated with T-cell mediated suppression of hematopoiesis, characteristics of T-cell clonal expansion in MDS patients, change of T-cell repertoire and recent thymus output function in MDS patients, efficiency of immunosuppressive treatment associated with T-cell clonal expansion in MDS patients and significance of T-cell clonal analysis in clinical application.
Clone Cells ; Humans ; Myelodysplastic Syndromes ; immunology ; Receptors, Antigen, T-Cell ; immunology ; T-Lymphocytes ; cytology ; immunology

Hematologic Neoplasms ; therapy ; Humans ; Immunotherapy, Adoptive ; Receptors, Antigen, T-Cell ; Receptors, IgG ; immunology ; T-Lymphocytes

Crystallography, X-Ray ; Receptors, Antigen, T-Cell ; chemistry ; immunology ; metabolism ; T-Lymphocytes ; immunology ; metabolism

T cell recognition of foreign peptide antigen and tolerance to self peptides is key to the proper function of the immune system. Usually, in the thymus T cells that recognize self MHC + self peptides are deleted and those with the potential to recognize self MHC + foreign peptides are selected to mature. However there are exceptions to these rules. Autoimmunity and allergy are two of the most common immune diseases that can be related to recognition of self. Many genes work together to lead to autoimmunity. Of those, particular MHC alleles are the most strongly associated, reflecting the key importance of MHC presentation of self peptides in autoimmunity. T cells specific for combinations of self MHC and self peptides may escape thymus deletion, and thus be able to drive autoimmunity, for several reasons: the relevant self peptide may be presented at low abundance in the thymus but at high level in particular peripheral tissues; the relevant self peptide may bind to MHC in an unusual register, not present in the thymus but apparent elsewhere; finally the relevant self peptide may be post translationally modified in a tissue specific fashion. In some types of allergy, the peptide + MHC combination may also be fully derived from self. However the combination in question may be modified by the presence of other ligands, such as small drug molecules or metal ions. Thus these types of allergies may act like the post translationally modified peptides involved some types of autoimmunity.
Animals ; Autoantigens ; immunology ; Autoimmunity ; HLA Antigens ; immunology ; Humans ; Hypersensitivity ; immunology ; Receptors, Antigen, T-Cell ; metabolism ; T-Lymphocytes ; immunology ; metabolism

GammadeltaT cells are considered as linkage between innate and adaptive immune response, which recognize specific antigen without MHC-restriction. Vgamma9Vdelta2T cells, isolated from peripheral blood and tumor tissue, can be activated by non-peptide phosphoantigen through binding to its gammadeltaTCR and proliferate under IL-2 stimulation. It has been shown that Vgamma9Vdelta2T cells possess anticancer activity against several types of tumor in vitro, as well as inhibit the growth of lymphoma, breast cancer and malignant melanoma in vivo. The phase I clinical trial of the application of Vgamma9Vdelta2T cells in treatment of lung cancer, renal cancer and prostate cancer demonstrated promising results. This review summarizes the recent advances in antigen recognition and activation of gammadeltaT cells, and the gammadeltaT cell-based immunotherapy for cancer treatment.
Humans ; Immunotherapy ; methods ; Immunotherapy, Adoptive ; methods ; Neoplasms ; immunology ; therapy ; Receptors, Antigen, T-Cell, gamma-delta ; immunology ; T-Lymphocyte Subsets ; immunology

T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR-engineered T cells to target New York esophageal squamous cell carcinoma (NY-ESO-1). These successes demonstrate the potential of this approach to treat cancer. In this review, we provide a perspective on the current and future applications of TCR-engineered T cells for the treatment of cancer. Our summary focuses on TCR activation and both pre-clinical and clinical applications of TCR-engineered T cells. We also discuss how to enhance the function of TCR-engineered T cells and prolong their longevity in the tumor microenvironment.
Animals ; Antigens, Neoplasm ; immunology ; metabolism ; Humans ; Neoplasms ; immunology ; metabolism ; Receptors, Antigen, T-Cell ; genetics ; metabolism ; T-Lymphocytes ; immunology ; metabolism

T cell can only recognize specific antigenic peptide-MHC complex on antigen-presenting cell. This is MHC restriction in antigen recognition of T cell. This phenomenon was discovered by an Austrian scientist Peter. C. Doherty and a Swedish scientist Rolf. M. Zinkernagel by chance. Then, in order to explain the phenomenon, they proposed two hypotheses: dual receptor and modified self. In the during following 20 years numbers of scientists spent great amount of time in the study of the phenomenon. The process of cell-mediated immune response becomes clear, which greatly promotes the advancing of immunology and many related disciplines.
Animals ; Antigen-Presenting Cells ; immunology ; Epitopes ; immunology ; Humans ; Immunity, Cellular ; Major Histocompatibility Complex ; immunology ; Receptors, Antigen, T-Cell ; immunology ; T-Lymphocytes ; immunology

In order to analyze the distribution and clonal expansion of TCR Vbeta subfamily T cells in patients with acute promyelocytic leukemia (APL) in vivo and in vitro after T cell culture, the peripheral blood mononuclear cells from 3 APL patients were expanded by rhIL-2 and anti-CD3 antibody using liquid T lymphocytes culture technique. The complementary determining region 3 (CDR3) of TCR beta with variable region genes was amplified in T cells from 3 APL cases before and after T cell culture by using RT-PCR. The positive products were further analyzed to identify the clonality of T cells by genescan. The results showed that only a part of 24 Vbeta subfamilies was detected in T cells from the patients, and some Vbeta subfamily T cells could be identified after T cells culture. The clonal expansion T cells in some TCR Vbeta subfamilies could be found in all patients. The similar oligoclonal expansion of Vbeta1, Vbeta3, Vbeta7, Vbeta16 and Vbeta20 T cells was detected in two cases at different time points after T cell culture. It is concluded that the restricted expression of TCR Vbeta subfamily in T cells from patients might be the common feature in leukemia. Some Vbeta subfamily T cells could be induced after T cells culture in vitro. The continual clonal expansion of TCR Vbeta subfamily T cells at different time points after T cells culture could be a specific immune response of patients T cells related to the specific APL cell associated antigen.
Humans ; Leukemia, Promyelocytic, Acute ; genetics ; immunology ; Lymphocyte Activation ; Receptors, Antigen, T-Cell, alpha-beta ; genetics ; T-Lymphocytes ; immunology

To understand the characteristics of T cell receptors recognizing antiphospholipid syndrome associated antigen, the characteristics of T cells were analyzed using T cell receptor beta variable region (TCRbetaV) gene spectrotyping in a case of antiphospholipid syndrome (APS). The results indicated that in the case of APS there were 2 dominant T cell clones. The TCRbetaVs sequences of the 2 T cell clones showed the TCRbetaVs belonged to 8 and 23 gene families respectively. The peptides of third complementarity-determining regions (CDR3) in the TCRbetaVs were CASSLLVAGGPRAYNEQFFGPG and CASSLAGFGQPQHFGDG. Comparing the motifs in CDR3 with another autoimmune disease, the motif YNEQFFGPG in TCRbetaV8 and motif QHFGDG in TCRbetaV23 were identical with that of idiopathic thrombocytopenic purpura and systemic lupus erythematosus reported before. In conclusion, some T cell clones proliferating in these autoimmune diseases may recognize the same antigens.
Adult ; Antiphospholipid Syndrome ; immunology ; Autoantigens ; immunology ; Female ; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor ; immunology ; Genes, T-Cell Receptor beta ; genetics ; immunology ; Humans ; Immunoglobulin Variable Region ; immunology ; Receptors, Antigen, T-Cell ; immunology

Chimeric antigen receptor (CAR) is a recombinant immunoreceptor combining an antibody-derived targeting fragment with signaling domains capable of activating cells, which endows T cells with the ability to recognize tumor-associated surface antigens independent of the expression of major histocompatibility complex (MHC) molecules. Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL)). Given this success, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.
Animals ; Humans ; Immunity, Cellular ; Immunotherapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; pathology ; therapy ; Receptors, Antigen, T-Cell ; immunology ; Recombinant Fusion Proteins ; immunology ; T-Lymphocytes ; immunology ; transplantation