Abstract The Melan-A/MART-1 gene, which is expressed by normal melanocytes as well most fresh melanoma samples and cell lines, codes for Ags recognized tumor-reactive CTL. HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A27-35 (AAGIGILTV) Melan-A26-35 (EAAGIGILTV) peptides. sequences of these two peptides are not necessarily optimal far binding to HLA-A*0201 concerned, since both lack one dominant anchor amino acid residues (leucine or methionine) at position 2. In...

Differences in the structure of interphase nucleus between two species birds, Japanese quail (Coturnix coturnix japonica) and chick (Gallus gallus) has been used to distinguish cells from different origins interspecies combinations. This biological cell marking technique was applied thymus histogenesis. Using various combinations components thymic rudiments, respective contribution endodermal epithelium, mesenchyme, blood-borne extrinsic elements histogenesis analyzed. It demonstrated that...

Inhibitors of the protease HIV-1 have been used successfully for treatment HIV-1-infected patients and AIDS disease. We tested whether these inhibitory drugs exerted effects in addition to their antiviral activity. Here, we show mice infected with lymphocytic choriomeningitis virus treated inhibitor ritonavir a marked inhibition cytotoxic T lymphocyte (CTL) activity impaired major histocompatibility complex class I-restricted epitope presentation absence direct on replication. A potential...

Subsets of T and natural killer (NK) lymphocytes express the CD94-NKG2A heterodimer, a receptor for major histocompatibility complex class I molecules. We show here that engagement heterodimer inhibits both antigen-driven tumor necrosis factor (TNF) release cytotoxicity on melanoma-specific human cell clones. Similarly, CD16-mediated NK is extinguished by cross-linking heterodimer. Combining in vivo vitro analysis, we report I/VxYxxL immunoreceptor tyrosine-based inhibition motifs (ITIM)...

A cytolytic T lymphocyte (CTL) clone that lyses many HLA-A2 melanomas was derived from a population of tumor-infiltrating lymphocytes an melanoma patient. The gene coding for the antigen recognized by this CTL identified transfection cDNA library. It is which has been reported to code N-acetylglucosaminyltransferase V (GnT-V). Remarkably, antigenic peptide encoded sequence located in intron. In contrast fully spliced GnT-V mRNA, found wide range normal and tumoral tissues, mRNA containing...

Abstract A PCR-based method that determines VDJ junction size patterns in 24 human TCR V beta subfamilies was used to analyze T cells infiltrating sequential malignant melanoma biopsies for the presence of clonal expansions. Infiltrating cell populations were found present expansions over a more or less complex polyclonal background. Two clones from single patient sequenced and detected three different tumor sites (skin biopsies), whereas only one them also peripheral blood. Biopsies this...

The entry and differentiation of lymphoid precursor cells (LPC) in grafted mouse fetal thymuses the emigration explants thymocytes has been followed a system which donor host lymphocytes could be distinguished on basis Thy-1 expression. It appears that LPC invade thymus between 10 13 days rapidly differentiate into positive thymocytes, giving rise to all populations both cortical medullary locations until approximately end first week after birth. Lymphoid enter life only 6 or 7 birth, when...

Abstract During analysis of CD8 T cells derived from ascites a colon cancer patient, we isolated Vγ9Vδ2 cell clone showing strong reactivity against autologous tumor lines. This killed large fraction allogeneic carcinoma and melanoma lines, but did not affect normal line, fibroblasts, or melanocytes. Tumor recognition was TCR NKG2D dependent induced TNF-α IFN-γ secretion by the clone; accordingly, targets expressed several ligands, such as MHC class I chain-related gene A UL16-binding...

The histogenesis of the bursa Fabricius and bone marrow was studied by a biological cell marking technique based on differences in nuclear structure two species birds, Japanese quail (Coturnix coturnix japonica) chick (Gallus gallus). In cells nucleus contains large amount heterochromatin associated with nucleolus. That makes it possible to distinguish them from after Feulgen-Rossenbeck staining electron microscopy. By grafting bursal rudiments limb buds into inversely demonstrate that whole...

Abstract HLA-E are nonclassical MHC molecules with poorly characterized tissue distribution and functions. Because of their capacity to bind the inhibitory receptor, CD94/NKG2A, expressed by NK cells CTL, might play an important role in immunomodulation. In particular, expression favor tumor cell escape from CTL immunosurveillance. To address potential melanoma immunobiology, we assessed these ex vivo human biopsies melanocyte lines. Melanoma lines no or low surface, but significant...

Gut bacterium Faecalibacterium prausnitzii activates a newly identified set of human IL-10-producing Treg cells (CD4CD8αα lymphocytes), revealing mechanism by which commensal microbes contribute to host immunity.

The human colonic mucosa contains regulatory type 1-like (Tr1-like, i.e. IL-10-secreting and Foxp3-negative) T cells specific for the gut Clostridium Faecalibacterium prausnitzii (F. prausnitzii), which are both decreased in Crohn's disease patients. These data, together with demonstration, mice, that (Treg) induced by bacteria key players colon homeostasis, support a similar role F. prausnitzii-specific Treg colon. Here we assessed mechanisms whereby induces Treg. We demonstrated...

The Melan-A/MART-1 gene product is frequently recognized by tumor-specific HLA-A2-restricted CTL. An immunodominant nonapeptide has been localized to the region spanning residues 27-35. However, decapeptide including 26-35 (the extended NH2 terminally one residue) appeared be as efficiently nonapeptide. In this study, we show that optimal length peptide appears correspond 26-35, assessed quantitative analyses of both 4 polyclonal and 13 monoclonal populations specific Functional assays...

Coculture of melanoma cells and T cell clones derived from tumor-infiltrating lymphocytes (TIL) generally results in lysis the antigen-bearing tumor but to inefficient proliferation IL-2 secretion by responder cells. This suboptimal activation is classically explained an inability provide costimulatory signals. Here we analyzed responses synthetic peptides HLA-A2.1-restricted CTL specific for antigens MART-1 NA17-A. We showed that peptide concentrations ranging 1 pM 10 nM efficiently...

Abstract The host immune response plays a major role in colorectal carcinoma (CRC) progression. A mechanism of tumor escape might involve expression the human leucocyte antigen (HLA)‐E/β2m on cells. inhibitory effect HLA‐E/β2m CD8+ cytotoxic T lymphocytes and natural killer (NK) cells is mediated by main HLA‐E receptor CD94/NKG2A. As pathophysiological relevance this CRC remains unknown, prompted us to examine, situ , series 80 ( i ) β2m coexpression cells, ii density CD8+, cytotoxic, CD244+...

Peptide splicing is a novel mechanism of production peptides relying on the proteasome and involving linkage fragments originally distant in parental protein. Peptides produced by can be presented class I molecules MHC recognized CTLs. In this study, we describe new antigenic peptide, which HLA-A3 comprises two noncontiguous melanoma differentiation Ag gp100(PMEL17) spliced together reverse order to that they appear Contrary previously described peptides, are association 3-6 aa, peptide work...

Abundance of Faecalibacterium prausnitzii, a dominant bacterium the human microbiota that exhibits antiinflammatory effects, is decreased in patients with inflammatory bowel diseases (IBD). In humans, colonic lamina propria contains IL-10-secreting, Foxp3- Tregs characterized by double expression CD4 and CD8α (DP8α) specificity for F. prausnitzii. This Treg subset IBD. The vivo effect DP8α cells has not been evaluated yet to our knowledge. Here, using humanized model NSG immunodeficient...

In this study, we have investigated the mRNA expression of cancer germ-line genes MAGE, BAGE, GAGE, RAGE and tumor-overexpressed gene PRAME by human myeloma cell lines malignant plasma cells from patients with multiple (MM). By reverse transcription-PCR, show that all (n = 16) express at least one these genes, except RAGE-1 was never expressed. We majority MM 21) expressed MAGE-1, MAGE-3 PRAME. On contrary, polyclonal reactive did not any genes. flow cytometry, mage-1 protein is within...

Abstract We show here that tumor infiltrating lymphocytes (TIL) derived from three renal carcinoma (RC) tumors, which developed in the same patient over a 3-yr period, were systematically enriched gamma delta + T cells (27-74%) after short term vitro culture. Analysis of repertoire TIL and PBL this patient, revealed predominant expression structurally diverse V 1 TCR by contrasting with classically dominant use 2 PBL. Functional analysis further showed that, independently genes expressed,...

Abstract In this study, we report the adoptive transfer of highly tumor-reactive Melan-A-specific T cell clones to patients with metastatic melanoma, and follow-up these injected cells. These were generated from HLA-A*0201 by in vitro stimulations total PBMC HLA-A*0201-binding Melan-A peptide analog ELAGIGILTV. Ten stage IV melanoma treated infusion CTL IL-2 IFN-α. The clones, effector/memory phenotype selected on basis their ability produce response Melan-A-positive lines. Infused detected,...