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HLA Class (hla + class)

Distribution by Scientific Domains
Medical Sciences100%

Terms modified by HLA Class

  • hla class i
  • hla class i allele
  • hla class i antigen
    		•
  • hla class i molecule
  • hla class ii
  • hla class ii allele
    		•
  • hla class ii gene
  • hla class ii molecule

    • Selected Abstracts

    The MHC class,II transactivator (CIITA) mRNA stability is critical for the HLA class,II gene expression in myelomonocytic cells

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2005
    Andrea De Lerma Barbaro
    Abstract The human promyelocytic U937 cells express detectable levels of MHC class,II (MHC-II) molecules. Treatment with 12-o- - tetradecanoyl phorbol 13-acetate (TPA), inducing macrophage-like differentiation, produces a dramatic decrease of MHC-II expression as result of down-modulation of the activation of immune response gene,1 (AIR-1)-encoded MHC-II transactivator (CIITA). This event is specific, as MHC class,I remains unaffected. Similar results are observed with U937 cells expressing an exogenous full-length CIITA. Molecular studies demonstrate that TPA treatment affects the stability of CIITA mRNA rather than CIITA transcription. Importantly, cis -acting elements within the distal 650,bp of the 1035-bp 3,,untranslated region (3,UTR, nucleotides 3509,4543) are associated to transcript instability. Transcription inhibitors actinomycin,D and 5,6-dichlororibofuranosyl benzimidazole, and the translation inhibitor cycloheximide significantly rescue the accumulation of CIITA mRNA in TPA-treated cells. A similar effect is also observed after treatment with staurosporine and the PKC-specific inhibitor GF109203X. The instability of CIITA mRNA produced by TPA in U937 cells is not seen in B,cells. These results demonstrate the presence of an additional level of control of MHC-II expression in the macrophage cell lineage depending upon the control of CIITA mRNA stability, most likely mediated by differentiation-induced, 3,UTR-interacting factors which require kinase activity for their destabilizing function. [source]

    Reconstitution of anti-HIV effector functions of primary human CD8 T,lymphocytes by transfer of HIV-specific ,,,TCR genes

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004
    Takamasa Ueno
    Abstract We redirected the antigen specificity of primary human CD8 T,cells by retrovirus-mediated transduction of genes encoding ,,,TCR specific to HIV-1 Pol protein. A large polyclonal population of TCR-transduced CD8 T,cells showed substantial cytotoxic and cytokine production activities toward target cells either pulsed with the peptide or infected with HIV-1, and their functional activities were comparable to those of the parental CTL clone. Peptide fine-specificity and promiscuous recognition of HLA class,I supertypes of the parental CTL clone were also preserved in the TCR-transduced cells. There were no signs of allogeneic responses in these cells, although hybrid TCR dimers consisting of transduced TCR and endogenous TCR were suspected to have been formed in these cells, as the effect of transgene expression on the surface expression of the desired TCR was limited. Moreover, the TCR-transduced cells showed potent inhibitory activity against HIV-1 replication in vitro, although the differential surface expression of the desired TCR resulted in differential functional avidity of individual TCR-transduced cells toward the peptide-pulsed target cells. These data suggest that the reconstitution of HIV-specific immunoreactive T,cells engineered by genetic transfer of HIV-specific TCR is a potential alternative to immunotherapeutic applications against HIV infections. [source]

    Differential effects of US2, US6 and US11 human cytomegalovirus proteins on HLA class,Ia and HLA-E expression: impact on target susceptibility to NK cell subsets

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2003
    Manuel Llano
    Abstract We compared in an inducible expression system the individual effect of US2, US6 and US11 human cytomegalovirus (HCMV) proteins on HLA-E and HLA class,Ia surface expression, assessing in parallel their influence on target susceptibility to NK cell clones. To this end, the RPMI,8866 B,lymphoma cell line (HLA-A2, HLA-A3, HLA-B7, HLA-Cw7, HLA-ER, HLA-EG) was stably cotransfected with the ecdysone receptor, together with the US sequences under the control of an ecdysone-inducible promoter. Biosynthesis of viral proteins was turned on by incubating transfectants with Ponasterone,A. US6 down-regulated expression of all class,I molecules, hampering target resistance to NK cell clones controlled by the CD94/NKG2A, KIR2DL2 and/or CD85j (ILT2 or LIR-1) inhibitory receptors. By contrast, US11 reduced the surface levels of class,Ia molecules but preserved HLA-E; this rendered US11+ cells sensitive to NK clones under the control of KIR2DL2 and/or CD85j, while their resistance to CD94/NKG2A+KIR2DL2, effector cells was maintained. US2 preserved as well HLA-E expression but selectively targeted class,Ia molecules; in fact, HLA-A and HLA-C allotypes were down-modulated whereas HLA-B7 remained unaltered. US2+ targets became sensitive to KIR2DL2+ cells but remained resistant to CD94/NKG2A+CD85j+ NK clones. The differential effects of US proteins on HLA class,Ia and HLA-E likely reflect the evolutionary adaptation of HCMV to counteract NK-mediated surveillance. [source]

    The ester-bonded palmitoyl side chains of Pam3CysSerLys4 lipopeptide account for its powerful adjuvanticity to HLA class,I-restricted CD8+ T,lymphocytes

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003
    Anca Reschner
    Abstract Molecularly defined adjuvants are urgently required to implement immunization protocols by which CD8+ T,cells induction is envisaged. We show here that the synthetic lipopeptide Pam3CysSerLys4 (P3CSK4) strongly enhances the expansion of antigen-specific IFN-,+CD8+ cells in vitro. These effects critically depend on the presence of two ester-bonded palmitoylated side chains. In fact, T,cell expansion is impaired in the presence of derivatives bearing two non-palmitoylated fatty acid chains, while derivatives with only one amide-bonded palmitoylated residue are completely inactive and behave like the non-lipidated peptide backbone. P3CSK4 is not mitogenic for T,lymphocytes and can modulte DC immune biological properties. Indeed, doses as low as 100,ng/ml increase CD86, CD83 and CD40 surface expression on DC, fail to induce CCR7, and trigger a defined pattern of soluble factors associated to immune effector functions. In particular, substantial amounts of TNF-,, IL-6, CCL2 and CXCL10, in the absence of IFN-,, IFN-,, IL-15, IL-12p70 and CX3CL1, can be measured. Accordingly, antigen-specific CD8+ T,cells expanded in vitro express CCR2 and CXCR3 chemokine receptors. Altogether our data suggest that human DC are able to respond to chemically different synthetic lipopeptide analogs and that optimal adjuvanticity to CD8+ T,cell induction is achieved by the palmitoylated structures. [source]

    Role of cytokine gene polymorphisms in acute rejection and renal impairment after liver transplantation

    LIVER TRANSPLANTATION, Issue 3 2001
    Julie R. Jonsson
    Although immunosuppressive regimens are effective, rejection occurs in up to 50% of patients after orthotopic liver transplantation (OLT), and there is concern about side effects from long-term therapy. Knowledge of clinical and immunogenetic variables may allow tailoring of immunosuppressive therapy to patients according to their potential risks. We studied the association between transforming growth factor-,, interleukin-10, and tumor necrosis factor , (TNF-,) gene polymorphisms and graft rejection and renal impairment in 121 white liver transplant recipients. Clinical variables were collected retrospectively, and creatinine clearance was estimated using the formula of Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain reaction-based methods. Thirty-seven of 121 patients (30.6%) developed at least 1 episode of rejection. Multivariate analysis showed that Child-Pugh score (P = .001), immune-mediated liver disease (P = .018), normal pre-OLT creatinine clearance (P = .037), and fewer HLA class 1 mismatches (P = .038) were independently associated with rejection. Renal impairment occurred in 80% of patients and was moderate or severe in 39%. Clinical variables independently associated with renal impairment were female sex (P = .001), pre-OLT renal dysfunction (P = .0001), and a diagnosis of viral hepatitis (P = .0008). There was a significant difference in the frequency of TNF-,-308 alleles among the primary liver diseases. After adjustment for potential confounders and a Bonferroni correction, the association between the TNF-,-308 polymorphism and graft rejection approached significance (P = .06). Recipient cytokine genotypes do not have a major independent role in graft rejection or renal impairment after OLT. Additional studies of immunogenetic factors require analysis of large numbers of patients with appropriate phenotypic information to avoid population stratification, which may lead to inappropriate conclusions. [source]

    Frequency of HLA class 1 and 2 alleles in Brazilian patients with AIDS and cytomegalovirus retinitis

    ACTA OPHTHALMOLOGICA, Issue 5 2003
    Maria De Lourdes Veronese Rodrigues
    Abstract. Purpose:,To evaluate the human leucocyte antigen (HLA) class 1 (HLA-A and HLA-B) and HLA class 2 (HLA-DRB1 and HLA-DQB1) allele profiles in the susceptibility to cytomegalovirus retinitis (CMV-R) in patients with AIDS. Methods:,Cytomegalovirus retinitis was clinically diagnosed by indirect binocular ophthalmoscopy. Human leucocyte antigens class 1 were typed using a complement-dependent microlymphocytotoxicity assay, and HLA class 2 alleles were identified using amplified DNA hybridized to sequence-specific oligonucleotide primers. Results:,The frequencies of HLA class 1 antigens and HLA class 2 alleles observed in patients and controls were similar; however, HLA-A31 antigen was over-represented in patients with AIDS, independent of the presence of CMV-R. Conclusion:,There was no association between HLA molecules/alleles and CMV-R in Brazilian patients with AIDS. However, the results support the role of the HLA system in the susceptibility to developing AIDS. [source]