Minor histocompatibility antigens are MHC-bound peptides and contribute to the generation of allo-responses after allogeneic transplantation. H60 is a dominant minor H antigen that induces a strong CD8 T-cell response in MHC-matched allogeneic transplantation settings. Here, we report establishment of a TCR transgenic mouse line named J15, wherein T cells express TCRs specific for H60 in complex with H-2K(b), and different fates of the thymocytes expressing J15 TCRs in various thymic antigenic environments. Thymocytes expressing the J15 TCRs were positively selected and differentiated into CD8+ single positive (SP) cells in the thymus of C57BL/6 mice, wherein the cognate antigen H60 is not expressed. However, thymocytes were negatively selected in thymus tissue where H60 was transgenically expressed under the control of the actin promoter, with double-positive stages of cells being deleted. Despite the ability of the H60H peptide (LTFHYRNL) variant to induce cytotoxic activity from H60-specific CTL lines at ~50% of the activity induced by normal H60 peptides (LTFNYRNL), J15-expressing thymocytes were positively selected in the thymus where the variant H60H was transgenically expressed. These results demonstrate that a single amino-acid change in the H60 epitope peptide influences the fate of thymocytes expressing the cognate TCR.
Actins ; Animals ; Histocompatibility Antigens* ; Histocompatibility* ; Mice ; Mice, Transgenic ; Minor Histocompatibility Antigens ; Peptides ; T-Lymphocytes ; Thymocytes* ; Thymus Gland ; Transplantation, Homologous

BACKGROUNDHumoral immunity is an important factor for long-term survival of renal allograft. Here we performed a four-year follow-up to explore the clinical significance of monitoring anti-human leukocyte antigens (HLA) and anti-major histocompatibility complex class I-related chain A (MICA) antibody expression after kidney transplantation.

METHODSWe obtained serial serum samples from 84 kidney transplant patients over a four-year period. All patients were followed up at least 6 months after transplantation and had at least two follow-up points. Anti-HLA and anti-MICA antibody titres and serum creatinine (SCr) levels were evaluated at each follow-up. Patients were divided into 4 groups: HLA(+) MICA(-), HLA(-)MICA(+), HLA(+)MICA(+) and HLA(-)MICA(-). The impact of post-transplant antibody level on kidney allograft function was evaluated.

RESULTSAntibodies were detected in 38.1% (32/84) of the renal allograft recipients. HLA, MICA and HLA+MICA expression was observed in 18.89%, 14.44% and 5.93% of the recipients respectively. The most frequent anti-HLA and anti-MICA specific antibodies identified were A11, A24, A29, A32, A33, A80; B7, B13, B37; DR17, DR12, DR18, DR52, DR53, DR1, DR4, DR9, DR51; DQ7, DQ4, DQ8, DQ2, DQ9, DQ5, DQ6 and MICA02, MICA18, MICA19, MICA07, MICA27. As the time after transplantation elapsed, more recipients developed de novo antibody expression. Total 11.91% (10/84) of the recipients had de novo antibody expression during the follow up. The average level of SCr and the percentage of recipients with abnormal allograft function were significantly higher in recipients with anti-HLA and/or anti-MICA antibody expression than those without. The appearance of anti-HLA and anti-MICA antibody expression always preceded the increase in SCr value.

CONCLUSIONSAnti-HLA and anti-MICA antibody expression has predictive value for early and late allograft dysfunction. The presence of donor specific antibody is detrimental to graft function and graft survival.

Female ; Follow-Up Studies ; Graft Survival ; HLA Antigens ; immunology ; Histocompatibility Antigens Class I ; immunology ; Humans ; Isoantibodies ; analysis ; Kidney Transplantation ; Male ; Minor Histocompatibility Antigens

GVHD (Graft-versus-Host Disease) results from the cytotoxic T lymphocytes from the bone marrow recognizing the recipient's minor histocompatibility antigens. In experimental murine models, either CD4+ or CD8+ T-cell subsets can cause GVHD, depending upon the particular strain combination utilized. Recent studies suggest that the keratinocyte undergo apoptosis in GVHD. However, morphological data supporting this concept are still lacking. The present study was undertaken in order to document apoptosis in experimental acute GVHD via sequential analysis of ultrastructure .Acute GVHD was produced across minor histocompatibility loci using appropriately matched murine strains. Acute GVHD was mediated with the use of highly purified preparations of donor CD4+ and CD8+ T-cell subsets. Whole T cells were used as a positive control and T cell depleted bone marrow as a negative control. Conventional transmission electron microscopy was used to define apoptosis structurally Sequential ultrastructure revealed that the keratinocyte underwent apoptosis in CD4+, CD8+ and whole T cell groups. This study demonstrates the sequential ultrastructure of the keratinocyte undergoing apoptosis from the beginning to the end. Both of the basal and the suprabasal keratinocytes show the morphology of early apoptosis, and the detachment of the tonofibril from the basement membrane and the adjacent cell was the general findings in the apoptotic cell Sequences of the cytoplasmic condensation was demonstrated . Through ultrastructural quantitation the apoptotic indices were depicted in all the experimental groups. Characteristically, numerous lymphocytes underwent apoptosis in CD8+ groups at day 28 and 35.
Apoptosis* ; Basement Membrane ; Bone Marrow Transplantation* ; Bone Marrow* ; Cytoplasm ; Epidermis* ; Humans ; Keratinocytes ; Lymphocytes ; Microscopy, Electron, Transmission ; Minor Histocompatibility Antigens ; Minor Histocompatibility Loci ; T-Lymphocyte Subsets ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic ; Tissue Donors

BACKGROUND: In the search for susceptibility genes responsible for leukemia, genetic studies involving HLA association have been in progress extensively since the first report on its effect on the disease. Here we investigated the genetic associations of different leukemias with 4 autosomal mHags, HA-1, -2, -8 and HB-1. In particular, HB-1 is one of the leukemia-associated minor histocompatibility antigens (mHags) that is significantly expressed by Epstein-Barr virus-transformed- and tumor cells of all B lineage acute lymphoblastic leukemia (ALL). METHODS: A simultaneous genotyping method using PCR sequence-specific primers against HA-1, -2, -8 and HB-1 was developed, and their allelic frequencies in 139 healthy controls and 36 leukemia patients were observed. To compare genotype, phenotype, and gene frequencies of mHags with healthy controls, leukemia patients were classified into sub groups of ALL, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). RESULTS: The genotype frequencies of HA-1, -2 and -8 were not significantly different from healthy controls in every group of leukemia patients. However, the HB-1 H genotype was significantly increased in leukemia patients (P=0.03, OR=1.82, CI=1.08~3.06), particularly in AML (P=0.01, OR=2.4, CI=1.21~4.76) as compared with healthy controls. CONCLUSION: Our results suggested that the genotype of HB-1 H may be associated with leukemia, particularly with AML. In further study, it is necessary to confirm the association of HB-1 with other leukemias in a larger group of patients, and to identify the underlying mechanism of HB-1 responsible for the occurrence of leukemia.
Gene Frequency ; Genotype* ; Humans ; Leukemia* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Minor Histocompatibility Antigens* ; Phenotype ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

OBJECTIVE: To explore the expression of IL-35, Epstein-Barr virus-induced gene 3 (EBI3) mRNA and IL-12A mRNA in peripheral blood of patients with allergic rhinitis and its significance. METHOD: Peripheral blood were collected from patients with allergic rhinitis (46 cases) and healthy human controls(30 cases). The level of IL-35 in serum was measured by enzyme-linked immunosorbent assay. The subunit EB13 and IL-12A of IL-35 mRNA expressions in peripheral blood mononuclear cell(PBMC) were detected by SYBR Green real-time quantitative PCR. RESULT: IL-35 level in AR group (251.22 +/- 46.27) ng/L was significantly lower compared with that in the normal control group (382.17 +/- 25.41) ng/L, (P < 0.01). The mRNA expression level of EBI3 in the patients with allergic rhinitis was significantly lower than that in the normal control group (P < 0.01), AR group EB13 mRNA level was about half of that in the normal control group. But the mRNA expression level of IL-12A in the patients with allergic rhinitis has not significant difference with that in the normal control group (P > 0. 05). CONCLUSION The decrease of IL-35 and EBI3 mRNA in AR,indicated that IL-35 and EBl3 mRNA may play an important role in allergic rhinitis.
Adolescent ; Adult ; Case-Control Studies ; Child ; Female ; Humans ; Interleukin-12 Subunit p35 ; blood ; Interleukins ; blood ; Male ; Middle Aged ; Minor Histocompatibility Antigens ; Rhinitis, Allergic ; blood ; Young Adult

BACKGROUND: Rapid platelet engraftment has several economic benefits by reducing the cost of supportive therapy as well as reducing the risk of fatal bleeding due to severe thrombocytopenia. Based on these considerations, we genotyped human platelet alloantigens (HPA) to evaluate the effect of minor transplantation antigen mismatches on the rate and speed of platelet recovery and clinical outcome of transplantation. METHODS: Thirty-five patients with various hematologic diseases transplanted between January 2001 and August 2004 were included. Genomic DNA was isolated from peripheral blood of donor-recipient pairs before transplantation. HPA-1, -2, -3, -4, -5, and -6 genotyping was performed by poly-merase chain reaction (PCR)-sequence specific primers (SSP). The effects of HPA compatibility on platelet recovery, incidences of graft-versus-host disease (GVHD) and relapse, and overall survival was investigated. RESULTS: There were no significant differences in platelet recovery according to HPA matching status. We observed no statistically significant differences in the occurrence of relapse and overall survival according to HPA-1, -2, and -3 matched/mismatched groups of patients, whereas HPA-3 mismatching was found to have a significant effect on GVHD development. There was also no difference in GVHD occurrence according to HPA-1 and -2 matched or mismatched transplants. CONCLUSIONS: Since platelet recovery in the HPA-1, -2, -3, and -5 matched/mismatched groups is not significantly different, the seems that platelet glycoprotein (GP) does not seem to act as a factor influencing the homing of hematopoietic stem cells. The finding that HPA-3 incompatibility may be involved in GVHD can be of importance. If a role for HPA-3 as minor histocompatibility antigens is confirmed by additional studies, we can ameliorate the outcome of allogeneic stem cell transplantation by typing of HPA and selecting the most closely related donors.
Antigens, Human Platelet ; Blood Platelets* ; DNA ; Glycoproteins ; Graft vs Host Disease* ; Hematologic Diseases ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells ; Hemorrhage ; Humans ; Incidence ; Minor Histocompatibility Antigens ; Recurrence ; Stem Cell Transplantation ; Thrombocytopenia ; Tissue Donors

Child, Preschool ; Cystathionine beta-Synthase ; genetics ; Folic Acid ; blood ; metabolism ; Genetic Predisposition to Disease ; Heart Defects, Congenital ; enzymology ; genetics ; Humans ; Infant ; Infant, Newborn ; Methylenetetrahydrofolate Dehydrogenase (NADP) ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Methyltransferases ; genetics ; Minor Histocompatibility Antigens ; Polymorphism, Genetic ; Risk Factors

In allogeneic transplantation, including the B6 anti-BALB.B settings, H60 and H4 are two representative dominant minor histocompatibility antigens that induce strong CD8 T-cell responses. With different distribution patterns, H60 expression is restricted to hematopoietic cells, whereas H4 is ubiquitously expressed. H60-specific CD8 T-cell response has been known to be dominant in most cases of B6 anti-BALB.B allo-responses, except in the case of skin transplantation. To understand the mechanism underlying the subdominance of H60 during allogeneic skin transplantation, we investigated the dynamics of the H60-specific CD8 T cells in B6 mice transplanted with allogeneic BALB.B tail skin. Unexpectedly, longitudinal bioluminescence imaging and flow cytometric analyses revealed that H60-specific CD8 T cells were not always subdominant to H4-specific cells but instead showed a brief dominance before the H4 response became predominant. H60-specific CD8 T cells could expand in the draining lymph node and migrate to the BALB.B allografts, indicating their active participation in the anti-BALB.B allo-response. Enhancing the frequencies of H60-reactive CD8 T cells prior to skin transplantation reversed the immune hierarchy between H60 and H4. Additionally, H60 became predominant when antigen presentation was limited to the direct pathway. However, when antigen presentation was restricted to the indirect pathway, the expansion of H60-specific CD8 T cells was limited, whereas H4-specific CD8 T cells expanded significantly, suggesting that the temporary immunodominance and eventual subdominance of H60 could be due to their reliance on the direct antigen presentation pathway. These results enhance our understanding of the immunodominance phenomenon following allogeneic tissue transplantation.
Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology/metabolism ; CD8-Positive T-Lymphocytes/*immunology ; Epitopes, T-Lymphocyte/*immunology ; Female ; Graft Rejection/*immunology ; Interferon-gamma ; Lymphocyte Activation/immunology ; Lymphocyte Count ; Mice ; Minor Histocompatibility Antigens/*immunology/metabolism ; *Skin Transplantation ; Transplantation, Homologous

PURPOSE: Numerous studies have assessed the association of SP110 gene variants with tuberculosis (TB), but the results were inconsistent. Through a comprehensive review and meta-analysis, our study aimed to clarify the nature of genetic risks contributed by 11 polymorphisms for the development of TB. MATERIALS AND METHODS: Through searching PubMed, web of science, China National Knowledge Infrastructure (CNKI) databases, a total of 11 articles including 13 independent studies were selected. The pooled odd ratios (ORs) along with their corresponding 95% confidence interval (CI) were estimated for allelic comparisons, additive model (homozygote comparisons; heterozygote comparisons), dominant model and recessive model. We also assessed the heterogeneity across the studies and publication bias. RESULTS: The results of combined analysis revealed a significantly increased risk of TB for single nucleotide polymorphism (SNP) rs9061 in all five comparisons (allelic comparisons: OR=1.28, 95% CI=1.14–1.44, p<0.0001; homozygote comparisons: OR=2.84, 95% CI=1.84–4.38, p<0.00001; heterozygote comparisons: OR=1.23, 95% CI=1.05–1.43, p=0.009; dominant model: OR=1.32, 95% CI=1.14–1.53, p=0.0003; recessive model: OR=2.26, 95% CI=1.18–4.34, p=0.01). In subgroup analysis, the risk of TB associated with SNP rs9061 appeared to be increased. Moreover, increased risk of TB was also found in Asian subgroup of SNP rs11556887, while decreased risk of TB appeared in large sample size subgroup of SNP rs1135791. No significant association was observed between other SNPs and the risk of TB. CONCLUSION: Our meta-analysis suggested that the variant of SNP rs9061 might be a risk factor for TB.
Alleles ; Asian Continental Ancestry Group/genetics ; China ; Confidence Intervals ; Genetic Predisposition to Disease ; Heterozygote ; Homozygote ; Humans ; Minor Histocompatibility Antigens/*genetics ; Nuclear Proteins/*genetics ; Odds Ratio ; *Polymorphism, Single Nucleotide ; Risk Factors ; Tuberculosis, Pulmonary/*genetics

OBJECTIVETo analyze the association of micoRNA-related genes DROSHA single nucleotide polymorphisms (SNP) rs10719 and rs6877842, DICER1 rs3742330and GEMIN4 rs3744741 with prognosis of T-cell lymphoma.

METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the genotypes of the above 4SNPs and their associations with complete remission (CR) rate and overall survival (OS) in 163 patients with TCL.

RESULTSPatients carrying the rs6877842 CG genotype had a significantly higher CR rate compared with those carrying the CC genotype (OR=0.07, 95% CI 0.01-0.72, P=0.026); the same for patients carrying the DICER1 rs3742330 GG genotype compared with those carrying the GA genotype (OR=0.15, 95% CI 0.02-0.97, P=0.047) or the AA genotype (OR=0.11, 95% CI 0.02-0.71, P=0.020). In addition, patients with the DICER1 rs3742330 GG genotype had a significantly improved OS compared with those carrying the GA (HR=9.02, 95% CI 1.22-66.92, P=0.031) or AA genotype (HR=8.77, 95% CI 1.19-64.67, P=0.033). The other two SNPs of rs10719 and rs3744741 had no significant association with CR or OS.

CONCLUSIONDROSHA rs6877842 and DICER1 rs3742330 were independent factors for TCL CR, and DICER1 rs3742330 was also an independent prognostic factor for TCL OS.

DEAD-box RNA Helicases ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lymphoma, T-Cell ; diagnosis ; genetics ; MicroRNAs ; genetics ; Minor Histocompatibility Antigens ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Prognosis ; Ribonuclease III ; genetics ; Ribonucleoproteins, Small Nuclear ; genetics