Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 92
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Clin Exp Immunol ; 187(1): 124-137, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27324616

RESUMEN

CD4+ T helper cells are a valuable component of the immune response towards cancer. Unfortunately, natural tumour-specific CD4+ T cells occur in low frequency, express relatively low-affinity T cell receptors (TCRs) and show poor reactivity towards cognate antigen. In addition, the lack of human leucocyte antigen (HLA) class II expression on most cancers dictates that these cells are often unable to respond to tumour cells directly. These deficiencies can be overcome by transducing primary CD4+ T cells with tumour-specific HLA class I-restricted TCRs prior to adoptive transfer. The lack of help from the co-receptor CD8 glycoprotein in CD4+ cells might result in these cells requiring a different optimal TCR binding affinity. Here we compared primary CD4+ and CD8+ T cells expressing wild-type and a range of affinity-enhanced TCRs specific for the HLA A*0201-restricted NY-ESO-1- and gp100 tumour antigens. Our major findings are: (i) redirected primary CD4+ T cells expressing TCRs of sufficiently high affinity exhibit a wide range of effector functions, including cytotoxicity, in response to cognate peptide; and (ii) optimal TCR binding affinity is higher in CD4+ T cells than CD8+ T cells. These results indicate that the CD4+ T cell component of current adoptive therapies using TCRs optimized for CD8+ T cells is below par and that there is room for substantial improvement.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Vacunas contra el Cáncer/inmunología , Terapia Genética/métodos , Antígeno HLA-A2/inmunología , Inmunoterapia Adoptiva/métodos , Neoplasias/terapia , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Antígenos de Neoplasias/metabolismo , Línea Celular , Citotoxicidad Inmunológica , Humanos , Proteínas de la Membrana/metabolismo , Neoplasias/inmunología , Unión Proteica , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Transgenes/genética , Antígeno gp100 del Melanoma/metabolismo
2.
Clin Exp Immunol ; 180(2): 255-70, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25496365

RESUMEN

Antigen-specific T cell receptor (TCR) gene transfer via patient-derived T cells is an attractive approach to cancer therapy, with the potential to circumvent immune regulatory networks. However, high-affinity tumour-specific TCR clonotypes are typically deleted from the available repertoire during thymic selection because the vast majority of targeted epitopes are derived from autologous proteins. This process places intrinsic constraints on the efficacy of T cell-based cancer vaccines and therapeutic strategies that employ naturally generated tumour-specific TCRs. In this study, we used altered peptide ligands and lentivirus-mediated transduction of affinity-enhanced TCRs selected by phage display to study the functional properties of CD8(+) T cells specific for three different tumour-associated peptide antigens across a range of binding parameters. The key findings were: (i) TCR affinity controls T cell antigen sensitivity and polyfunctionality; (ii) supraphysiological affinity thresholds exist, above which T cell function cannot be improved; and (iii) T cells transduced with very high-affinity TCRs exhibit cross-reactivity with self-derived peptides presented by the restricting human leucocyte antigen. Optimal system-defined affinity windows above the range established for natural tumour-specific TCRs therefore allow the enhancement of T cell effector function without off-target effects. These findings have major implications for the rational design of novel TCR-based biologics underpinned by rigorous preclinical evaluation.


Asunto(s)
Antígenos de Neoplasias/inmunología , Linfocitos T CD8-positivos/inmunología , Proteínas de Neoplasias/inmunología , Neoplasias/inmunología , Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Antígenos de Neoplasias/genética , Linfocitos T CD8-positivos/patología , Línea Celular Tumoral , Humanos , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/patología , Péptidos/genética , Receptores de Antígenos de Linfocitos T/genética
3.
Tissue Antigens ; 77(3): 229-34, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21299528

RESUMEN

Myelin basic protein (MBP) is a candidate autoantigen in multiple sclerosis (MS). The immunodominant epitope for T-cell responses is assigned to the amino acid sequence MBP84-102, which binds to human leukocyte antigen (HLA)-DR2a (DRB5*0101) and HLA-DR2b (DRB1*1501) of the HLA-DR2 haplotype carrying the strongest genetic association with MS. In contrast with HLA-DR and -DQ molecules, HLA-DP molecules are poorly characterized with respect to the binding of self-peptides. We show here that HLA-DP2 binds MBP85-99 with high affinity, and that the amino acid residues in position MBP91, MBP92 and MBP93 are influencing the binding, as shown by alanine scans. We further used a series of truncated peptides to identify the core of the binding. Moving the frame along the peptide from residues 87-97 to 89-99 progressively decreased the binding affinity for HLA-DP2, while moving further towards the C-terminal completely abrogated the binding of peptides to HLA-DP2. The data suggest that the docking of the MBP85-99 peptide into the HLA-DP2 groove is dependent on MBP88V and MBP89V and may use either of them as primary anchor for the p1 position. HLA-DP2 might thus present the MBP85-99 peptide in the same register as the HLA-DRB1*1501, where the MBP89V is preferred as the p1 anchor. Notably, full-length MBP was able to compete for peptide binding with an affinity similar to that seen for the high-affinity binding peptides, DRα170-83 and IIP53-65. In summary, the HLA-DP2 molecule binds the immunodominant epitope in MS, MBP85-99, possibly in more than one register.


Asunto(s)
Antígenos HLA-DP/metabolismo , Epítopos Inmunodominantes/metabolismo , Proteína Básica de Mielina/metabolismo , Fragmentos de Péptidos/metabolismo , 1-Butanol/farmacología , Secuencia de Aminoácidos , Animales , Células Cultivadas , Drosophila melanogaster , Ensayo de Inmunoadsorción Enzimática , Antígenos HLA-DP/química , Antígenos HLA-DP/inmunología , Antígenos HLA-DP/aislamiento & purificación , Cadenas beta de HLA-DP , Humanos , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Proteína Básica de Mielina/inmunología , Fragmentos de Péptidos/inmunología , Unión Proteica/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato
4.
Nat Med ; 5(4): 399-404, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10202928

RESUMEN

The CD8 co-receptor is important in the differentiation and selection of class I MHC-restricted T cells during thymic development, and in the activation of mature T lymphocytes in response to antigen. Here we show that soluble CD8alphaalpha receptor, despite an extremely low affinity for MHC, inhibits activation of cytotoxic lymphocytes by obstructing CD3 zeta-chain phosphorylation. We propose a model for this effect that involves interference of productive receptor multimerization at the T-cell surface. These results provide new insights into the mechanism of T-cell activation and evidence that CD8 function is exquisitely sensitive to disruption, an effect that might be exploited by molecular therapeutics.


Asunto(s)
Antígenos CD8/farmacología , Activación de Linfocitos/efectos de los fármacos , Modelos Inmunológicos , Linfocitos T Citotóxicos/efectos de los fármacos , Complejo CD3/metabolismo , Antígenos CD8/inmunología , Dimerización , Antígenos de Histocompatibilidad Clase I/inmunología , Ligandos , Activación de Linfocitos/inmunología , Complejo Mayor de Histocompatibilidad , Péptidos/inmunología , Péptidos/farmacología , Fosforilación , Conformación Proteica , Receptores de Antígenos de Linfocitos T/inmunología , Transducción de Señal , Solubilidad , Linfocitos T Citotóxicos/inmunología
5.
J Exp Med ; 184(6): 2279-86, 1996 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-8976183

RESUMEN

In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael. 1986. Cell. 44:959-968). Altered peptide ligands (APLs) which antagonise CTL recognition of infected cells have been reported (Jameson, S.C., F.R. Carbone, and M.J. Bevan. 1993. J. Exp. Med. 177:1541-1550). In one example, lysis of antigen presenting cells by CTLs in response to recognition of an HLA B8-restricted HIV-1 P17 (aa 24-31) epitope can be inhibited by naturally occurring variants of this peptide, which act as TCR antagonists (Klenerman, P., S. Rowland Jones, S. McAdam, J. Edwards, S. Daenke, D. Lalloo, B. Koppe, W. Rosenberg, D. Boyd, A. Edwards, P. Giangrande, R.E. Phillips, and A. McMichael. 1994. Nature (Lond.). 369:403-407). We have characterised two CTL clones and a CTL line whose interactions with these variants of P17 (aa 24-31) exhibit a variety of responses. We have examined the high resolution crystal structures of four of these APLs in complex with HLA B8 to determine alterations in the shape, chemistry, and local flexibility of the TCR binding surface. The variant peptides cause changes in the recognition surface by three mechanisms: changes contributed directly by the peptide, effects transmitted to the exposed peptide surface, and induced effects on the exposed framework of the peptide binding groove. While the first two mechanisms frequently lead to antagonism, the third has more profound effects on TCR recognition.


Asunto(s)
Productos del Gen gag/inmunología , VIH-1/inmunología , Antígeno HLA-B8/biosíntesis , Antígeno HLA-B8/química , Fragmentos de Péptidos/inmunología , Conformación Proteica , Linfocitos T Citotóxicos/inmunología , Secuencia de Aminoácidos , Línea Celular , Células Clonales , Gráficos por Computador , Cristalografía por Rayos X , Variación Genética , Humanos , Inmunidad Celular , Estructura Secundaria de Proteína
6.
Mol Cell Biol ; 8(11): 5040-2, 1988 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-3062378

RESUMEN

We measured the binding of yeast heat shock factor (HSF) to DNA in vivo by using an interference assay in which HSF excludes GAL4 from a synthetic promoter element containing overlapping binding sites for each protein. The results show that HSF binds to DNA in unstressed cells and that binding is not sufficient for transcriptional activation.


Asunto(s)
ADN de Hongos/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas de Choque Térmico/metabolismo , Secuencia de Bases , Sitios de Unión , ADN de Hongos/genética , Proteínas Fúngicas/genética , Proteínas de Choque Térmico/genética , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
7.
Mol Cell Biol ; 16(7): 3866-77, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8668204

RESUMEN

The functional domain structure of human DNA topoisomerase IIalpha and Saccharomyces cerevisiae DNA topoisomerase II was studied by investigating the abilities of insertion and deletion mutant enzymes to support mitotic growth and catalyze transitions in DNA topology in vitro. Alignment of the human topoisomerase IIalpha and S. cerevisiae topoisomerase II sequences defined 13 conserved regions separated by less conserved or differently spaced sequences. The spatial tolerance of the spacer regions was addressed by insertion of linkers. The importance of the conserved regions was assessed through deletion of individual domains. We found that the exact spacing between most of the conserved domains is noncritical, as insertions in the spacer regions were tolerated with no influence on complementation ability. All conserved domains, however, are essential for sustained mitotic growth of S. cerevisiae and for enzymatic activity in vitro. A series of topoisomerase II carboxy-terminal truncations were investigated with respect to the ability to support viability, cellular localization, and enzymatic properties. The analysis showed that the divergent carboxy-terminal region of human topoisomerase IIalpha is dispensable for catalytic activity but contains elements that specifically locate the protein to the nucleus.


Asunto(s)
ADN-Topoisomerasas de Tipo II/química , ADN-Topoisomerasas de Tipo II/metabolismo , Saccharomyces cerevisiae/enzimología , Secuencia de Aminoácidos , Secuencia de Bases , Sitios de Unión , Secuencia Conservada , ADN-Topoisomerasas de Tipo II/biosíntesis , Humanos , Datos de Secuencia Molecular , Mutagénesis , Mutagénesis Insercional , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Eliminación de Secuencia
8.
Protein Sci ; 7(5): 1245-9, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9605330

RESUMEN

A strategy for overexpression in Escherichia coli of the extracellular immunoglobulin domain of human CD8alpha was devised using codon usage alterations in the 5' region of the gene, designed so as to prevent the formation of secondary structures in the mRNA. A fragment of CD8alpha, comprising residues 1-120 of the mature protein, excluding the signal peptide and the membrane-proximal stalk region, was recovered from bacterial inclusion bodies and refolded to produce a single species of homodimeric, soluble receptor. HLA-A2 heavy chain, beta2-microglobulin and a synthetic peptide antigen corresponding to the pol epitope from HIV-1 were also expressed in E. coli, refolded and purified. CD8alpha/HLA-A2 complexes were formed in solution and by co-crystallization with a stoichiometry of one CD8alpha alpha dimer to one HLA-A2-peptide unit.


Asunto(s)
Antígeno HLA-A2/química , Receptores de Antígenos de Linfocitos T alfa-beta/química , Animales , Células CHO , Cricetinae , Cristalización , Dimerización , Escherichia coli/genética , Antígeno HLA-A2/genética , Humanos , Insectos , Espectrometría de Masas , Pliegue de Proteína , Receptores de Antígenos de Linfocitos T alfa-beta/genética
9.
Protein Sci ; 7(5): 1264-6, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9605335

RESUMEN

HLA-E is the first human class Ib major histocompatibility complex molecule to be crystallized. HLA-E is highly conserved and almost nonpolymorphic, and has recently been shown to be the first specialized ligand for natural killer cell receptors. In functional studies, HLA-E is unlike the class Ia MHC molecules in having tightly restricted peptide binding specificity. HLA-E binds a limited set of almost identical leader sequence peptides derived from class Ia molecules and presents these at the cell surface for recognition by natural killer cell receptors. We now show that the extracellular region of HLA-E forms a stable complex with beta2 microglobulin and can be refolded around synthetic peptide. Crystals of this complex formed slowly over four to six months in the presence of ammonium sulphate. The crystals diffract to 2.85 A with space group P3(1)21 and unit cell dimensions a = 182.2 A, b = 182.2 A, c = 88.4 A.


Asunto(s)
Antígenos HLA/química , Antígenos de Histocompatibilidad Clase I/química , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Cristalografía por Rayos X , Cartilla de ADN , Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Conformación Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Antígenos HLA-E
10.
Protein Sci ; 8(11): 2418-23, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10595544

RESUMEN

A method to produce alphabeta T-cell receptors (TCRs) in a soluble form suitable for biophysical analysis was devised involving in vitro refolding of a TCR fusion protein. Polypeptides corresponding to the variable and constant domains of each chain of a human and a murine receptor, fused to a coiled coil heterodimerization motif from either c-Jun (alpha) or v-Fos (beta), were overexpressed separately in Escherichia coli. Following recovery from inclusion bodies, the two chains of each receptor were denatured, and then refolded together in the presence of denaturants. For the human receptor, which is specific for the immunodominant influenza A HLA-A2-restricted matrix epitope (M58-66), a heterodimeric protein was purified in milligram yields and found to be homogeneous, monomeric, antibody-reactive, and stable at concentrations lower than 1 microM. Using similar procedures, analogous results were obtained with a murine receptor specific for an influenza nucleoprotein epitope (366-374) restricted by H2-Db. Production of these receptors has facilitated a detailed analysis of viral peptide-Major Histocompatibility Complex (peptide-MHC) engagement by the TCR using both surface plasmon resonance (SPR) and, in the case of the human TCR, isothermal titration calorimetry (ITC) (Willcox et al., 1999). The recombinant methods described should enable a wide range of TCR-peptide-MHC interactions to be studied and may also have implications for the production of other heterodimeric receptor molecules.


Asunto(s)
Receptores de Antígenos de Linfocitos T alfa-beta/química , Secuencia de Aminoácidos , Sitios de Unión , Biofisica/métodos , Dimerización , Antígeno HLA-A2/química , Humanos , Leucina Zippers , Ligandos , Complejo Mayor de Histocompatibilidad , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas Oncogénicas v-fos/química , Conformación Proteica , Desnaturalización Proteica , Pliegue de Proteína , Proteínas Proto-Oncogénicas c-jun/química , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Solubilidad , Resonancia por Plasmón de Superficie
11.
FEBS Lett ; 383(1-2): 119-23, 1996 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-8612777

RESUMEN

Major histocompatibility complex class I B alleles, HLA B8, B53 and B3501 have been cloned, expressed, refolded and crystallized in specific complexes with a number of different 8-mer and 9-mer peptides. For some of these crystallization was initiated by cross-seeding between different B allele complexes. All crystallize in the space group P212121, with similar unit cell dimensions of approximately 52 A X 81 A X 112 A, contain one complex per asymmetric unit and diffract to approximately 2.0 A resolution.


Asunto(s)
Alelos , Genes MHC Clase I/genética , Antígenos HLA/química , Antígeno HLA-B8/química , Oligopéptidos/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Cristalización , Cristalografía por Rayos X , Cartilla de ADN , Electroforesis en Gel de Poliacrilamida , Epítopos/química , Escherichia coli/genética , Antígenos HLA/genética , Antígenos HLA/metabolismo , Antígeno HLA-B8/genética , Antígeno HLA-B8/metabolismo , Humanos , Datos de Secuencia Molecular , Oligopéptidos/química , Conformación Proteica , Pliegue de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo
12.
J Immunol Methods ; 89(2): 279-85, 1986 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-3517179

RESUMEN

A standard complement-dependent microcytotoxicity (CDC) technique was used for quantitative analysis of T-lymphocyte subsets in human peripheral blood and the results compared to those obtained by indirect immunofluorescence microscopy and flow cytometry. The monoclonal antibodies OKT3, OKT4 and OKT8 were used in the CDC method for detection of total-T cells, T-helper and T-suppressor cells respectively. The CDC technique provided reproducible results (CV, 3-7%) correlating well with both immunofluorescence techniques. This observation was valid both for healthy persons (n = 21) and for patients (n = 10) with immunological disorders. The correct antibody dilution, correction for background and the use of eosin staining are considered critical for the usefulness of this technique. The method has several advantages: it is widely used for histocompatibility testing, only simple equipment is necessary, and the amount of monoclonal antibody required per test is small.


Asunto(s)
Pruebas Inmunológicas de Citotoxicidad/métodos , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Linfocitos T/clasificación , Anticuerpos Monoclonales , Proteínas del Sistema Complemento/fisiología , Humanos , Recuento de Leucocitos , Microscopía Fluorescente
13.
Transplantation ; 39(1): 18-21, 1985 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-2578235

RESUMEN

We have analyzed the predictive value on cadaver kidney graft survival of a low stabilized relative response (SRR) in donor-specific mixed lymphocyte culture (MLC). Thirty-eight recipients and donors of cadaver kidneys constituted the case material. The 12-month survival of cadaveric grafts was 83% when the SRR values of the mixed lymphocyte reaction (MLR) between recipient and donor were below or equal to 50 and 40% when the SRR values were above 50. The difference was statistically significant (P less than 0.006). A higher (though not significantly so) graft survival rate was obtained in transplant groups when the recipients and donors were well matched for DR antigens. The 12-month survival was 70% when no DR incompatibilities could be demonstrated and 50% when one or more DR antigens were incompatible. The primary role of MLR matching for the outcome of kidney graft survival is supported by the observation that the influence of the MLR is still significant when stratified for DR matching (P less than 0.05). In conclusion, when adequately stabilized, the specific MLC reactivity of the recipient against the donor is a very important predictive factor for the outcome of cadaver kidney transplantation, which stresses the importance of improvements in serological DR typing.


Asunto(s)
Supervivencia de Injerto , Antígenos de Histocompatibilidad Clase II/análisis , Trasplante de Riñón , Prueba de Cultivo Mixto de Linfocitos , Donantes de Tejidos , Pruebas Inmunológicas de Citotoxicidad/métodos , Epítopos , Antígenos HLA-DR , Prueba de Histocompatibilidad , Humanos , Prueba de Cultivo Mixto de Linfocitos/métodos
14.
Hum Immunol ; 2(4): 333-40, 1981 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-6168620

RESUMEN

A typing system for HLA-D/DR-associated PLT-defined determinants, which have been called "DP" antigens, is reported. Some of the results concerning a data interpretation system, the reproducibility of PLT results, and the correlations between the results of HLA-D, -DR, and DP typing are presented. Also, a "new" human alloantigen, EP1, not belonging to the series of DP antigens, is defined with PLT.


Asunto(s)
Prueba de Histocompatibilidad/métodos , Isoantígenos , Linfocitos/inmunología , Epítopos , Antígenos de Histocompatibilidad Clase II , Humanos
15.
Hum Immunol ; 30(1): 27-31, 1991 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1672123

RESUMEN

The restriction fragment length polymorphism of the two human HLA-B-associated transcripts (BATs) genes, BAT1 and BAT2, identifying polymorphic bands of 12, 8, 2.5, and 1.1 kb, and at 3.3, 2.7, 2.3, and 0.9 kb, respectively, was investigated in patients with primary biliary cirrhosis (PBC), systemic lupus erythematosus (SLE), pauciarticular juvenile rheumatoid arthritis (P-JRA), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS), and in healthy Danes. The BAT2/RsaI 2.7-kb band fragment was more frequent in PBC, pSS, and SLE than in controls, but the p values did not reach significance when corrected for multiple comparisons. For pSS and SLE, the associations may be secondary to primary associations with HLA-B8 because the BAT2/RsaI 2.3-kb band, which is allelic to the BAT2/RsaI 2.7-kb band, is strongly negatively associated with HLA-B8 and HLA-DR3. The only significance obtained shows that the HLA-B8 frequency is increased in BAT2/RsaI 2.7-kb positive pSS patients as compared to the corresponding controls indicating that the HLA-B8 association may be strongest. No missing or extra DNA fragments were observed in the disease groups when compared with controls indicating that gross deletions or duplications of the BAT1 and BAT2 genes in the patients are unlikely. In conclusions, it cannot be excluded that the BAT2/RsaI 2.7-kb band may contribute to the susceptibility to PBC, pSS, and SLE.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Antígenos HLA-B/genética , Enfermedades Autoinmunes/genética , Marcadores Genéticos , Humanos , Cirrosis Hepática Biliar/genética , Cirrosis Hepática Biliar/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Polimorfismo de Longitud del Fragmento de Restricción , Síndrome de Sjögren/genética , Síndrome de Sjögren/inmunología , Transcripción Genética
16.
Hum Immunol ; 25(2): 135-48, 1989 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-2525543

RESUMEN

Recently, much interest has focused on the role of HLA class II antigens in T cell-T cell interactions. We have studied the stimulatory capability in the primary mixed leukocyte reaction and the primed lymphocyte reaction of 11 alloactivated, HLA-DR- or -DP-reactive CD4-positive T-cell lines (Ta). From 70 to 90% of the Ta were HLA class II-positive as judged by the reactions with HLA class II-reactive monoclonal antibodies, and the Ta carried the DR allospecificities of the original T-cell donor when typed in the microcytotoxic test using DR-specific alloantisera. Neither irradiated nor nonirradiated Ta stimulated primed lymphocytes directed against the relevant HLA class II antigens on the Ta. Interferon-gamma, recombinant interleukin 1, phorbol myristate acetate, calcium ionophore, and adherent cells had no effect on the stimulatory capability of Ta. The ability of irradiated Ta to stimulate in the primary mixed leukocyte reaction (median counts per minute (cpm) 5.5 x 10(3] was significantly lower than that of peripheral blood mononuclear cells (cpm: 44.0 x 10(3]. The stimulation by Ta was almost only seen when the Ta were specifically directed against the class II antigens of the responder peripheral blood mononuclear cells (i.e., in combinations with "backstimulation") (median cpm: 21,000). In mixed leukocyte reaction combinations without backstimulation, significantly weaker reactions were seen (median cpm: 1,000). This observation may explain previous controversies concerning the stimulatory capacity of Ta. Recombinant interleukin 2 significantly enhanced the very low mixed leukocyte culture responses induced by class II-incompatible Ta in combinations without backstimulation but had no significant effect on cultures with Ta autologous to the responder peripheral blood mononuclear cells. Thus, allogeneic class II-positive Ta can induce interleukin 2 responsiveness but lack accessory cell function(s) necessary for the induction of interleukin 2 production in primed and unprimed T cells.


Asunto(s)
Antígenos de Histocompatibilidad Clase II/inmunología , Interleucina-2/inmunología , Prueba de Cultivo Mixto de Linfocitos , Linfocitos T/inmunología , Anticuerpos Monoclonales , Células Presentadoras de Antígenos/inmunología , Antígenos de Superficie/análisis , Línea Celular , Separación Celular , Citometría de Flujo , Humanos
17.
Dis Markers ; 8(3): 113-6, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2148714

RESUMEN

We studied the distribution of HLA-DP antigens in 74 HIV-infected Danish homosexual men and 188 ethnically matched healthy individuals, using the primed lymphocyte typing (PLT) technique. Forty of the patients developed AIDS within 3 years after diagnosis, whereas the remaining 34 were healthy or had only minor symptoms for 3 years or more (median observation time was 42 months). HLA-DPwl seemed to be decreased (relative risk = 0.3) in AIDS patients (5.0 per cent) when compared to patients with minor symptoms (14.7 per cent) and healthy controls (14.9 per cent). These differences were, however, not statistically significant. There were no other apparent deviations between patients (or subgroups of patients) and controls.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/inmunología , Infecciones por VIH/inmunología , Antígenos HLA-DP/análisis , Susceptibilidad a Enfermedades , Marcadores Genéticos , Humanos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Factores de Riesgo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA