RESUMEN

One nucleotide deletion in codon 15 of HLA-B*40:01:02:01 results in a novel null allele, HLA-B*40:510N.

Asunto(s)

Alelos , Exones , Prueba de Histocompatibilidad , Eliminación de Secuencia , Humanos , Secuencia de Bases , Análisis de Secuencia de ADN/métodos , Antígeno HLA-B40/genética , Codón , Antígenos HLA-B/genética

RESUMEN

The coding sequence of HLA-B*40:540N differs from HLA-B*40:02:01:01 by a non-synonymous nucleotide substitution in exon 3.

Asunto(s)

Alelos , Secuencia de Bases , Exones , Humanos , Codón , Prueba de Histocompatibilidad , Antígenos HLA-B/genética , Antígeno HLA-B40/genética , Alineación de Secuencia , Análisis de Secuencia de ADN , Donantes de Tejidos , Masculino , Persona de Mediana Edad

RESUMEN

One nucleotide substitution in codon 81 of HLA-B*40:01:01 results in a novel allele, HLA-B*40:400.

Asunto(s)

Alelos , Exones , Antígeno HLA-B40 , Haplotipos , Prueba de Histocompatibilidad , Humanos , Taiwán , Antígeno HLA-B40/genética , Secuencia de Bases , Codón , Análisis de Secuencia de ADN/métodos , Pueblo Asiatico/genética , Polimorfismo de Nucleótido Simple , Alineación de Secuencia , Antígenos HLA-B/genética

RESUMEN

Identification of two novel HLA alleles in Russian bone marrow donors.

Asunto(s)

Alelos , Donantes de Tejidos , Humanos , Federación de Rusia , Antígeno HLA-A2/genética , Antígeno HLA-A2/inmunología , Trasplante de Médula Ósea , Antígeno HLA-B40/genética , Antígeno HLA-B40/inmunología , Exones , Prueba de Histocompatibilidad , Médula Ósea , Análisis de Secuencia de ADN

RESUMEN

HLA-B*40:86 differs from B*40:06:01:03 by a single nucleotide exchange in exon 3.

Asunto(s)

Exones , Antígeno HLA-B40 , Humanos , Alelos , Secuencia de Bases , Pueblos del Este de Asia/genética , Prueba de Histocompatibilidad , Antígeno HLA-B40/genética , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN/métodos

RESUMEN

HLA-B*40:550 differs from HLA-B*40:01:02:01 by one nucleotide in exon 1.

Asunto(s)

Exones , Antígeno HLA-B40 , Prueba de Histocompatibilidad , Humanos , Alelos , Secuencia de Bases , Codón , Pueblos del Este de Asia , Antígeno HLA-B40/genética , Alineación de Secuencia , Análisis de Secuencia de ADN/métodos

RESUMEN

BACKGROUND: Human Papillomavirus type 18 (HPV18) is a high-risk HPV that is commonly associated with cervical cancer. HPV18 oncogenes E6 and E7 are associated with the malignant transformation of cells, thus the identification of human leukocyte antigen (HLA)-restricted E6/E7 peptide-specific CD8 + T cell epitopes and the creation of a HPV18 E6/E7 expressing cervicovaginal tumor in HLA-A2 transgenic mice will be significant for vaccine development. METHODS: In the below study, we characterized various human HLA class I-restricted HPV18 E6 and E7-specific CD8 + T cells mediated immune responses in HLA class I transgenic mice using DNA vaccines encoding HPV18E6 and HPV18E7. We then confirmed HLA-restricted E6/E7 specific CD8 + T cell epitopes using splenocytes from vaccinated mice stimulated with HPV18E6/E7 peptides. Furthermore, we used oncogenic DNA plasmids encoding HPV18E7E6(delD70), luciferase, cMyc, and AKT to create a spontaneous cervicovaginal carcinoma model in HLA-A2 transgenic mice. RESULTS: Therapeutic HPV18 E7 DNA vaccination did not elicit any significant CD8 + T cell response in HLA-A1, HLA-24, HLA-B7, HLA-B44 transgenic or wild type C57BL/6 mice, but it did generate a strong HLA-A2 and HLA-A11 restricted HPV18E7-specific CD8 + T cell immune response. We found that a single deletion of aspartic acid (D) at location 70 in HPV18E6 DNA abolishes the presentation of HPV18 E6 peptide (aa67-75) by murine MHC class I. We found that the DNA vaccine with this mutant HPV18 E6 generated E6-specific CD8 + T cells in HLA-A2. HLA-A11, HLA-A24 and HLA-b40 transgenic mice. Of note, HLA-A2 restricted, HPV18 E7 peptide (aa7-15)- and HPV18 E6 peptide (aa97-105)-specific epitopes are endogenously processed by HPV18 positive Hela-AAD (HLA-A*0201/Dd) cells. Finally, we found that injection of DNA plasmids encoding HPV18E7E6(delD70), AKT, cMyc, and SB100 can result in the development of adenosquamous carcinoma in the cervicovaginal tract of HLA-A2 transgenic mice. CONCLUSIONS: We characterized various human HLA class I-restricted HPV18 E6/E7 peptide specific CD8 + T cell epitopes in human HLA class I transgenic mice. We demonstrated that HPV18 positive Hela cells expressing chimeric HLA-A2 (AAD) do present both HLA-A2-restricted HPV18 E7 (aa7-15)- and HPV18 E6 (aa97-105)-specific CD8 + T cell epitopes. A mutant HPV18E6 that had a single deletion at location 70 obliterates the E6 presentation by murine MHC class I and remains oncogenic. The identification of these human MHC restricted HPV antigen specific epitopes as well as the HPV18E6/E7 expressing adenosquamous cell carcinoma model may have significant future translational potential.

Asunto(s)

Carcinoma Adenoescamoso , Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Vacunas de ADN , Animales , Ácido Aspártico , Linfocitos T CD8-positivos , Carcinoma Adenoescamoso/complicaciones , Epítopos de Linfocito T/genética , Femenino , Antígenos HLA-A , Antígeno HLA-A1 , Antígeno HLA-A11 , Antígeno HLA-A2/genética , Antígeno HLA-A24 , Antígeno HLA-B40 , Antígeno HLA-B44 , Antígeno HLA-B7 , Células HeLa , Papillomavirus Humano 18 , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/complicaciones , Péptidos , Proteínas Proto-Oncogénicas c-akt , Linfocitos T Citotóxicos , Vacunas de ADN/genética

RESUMEN

BACKGROUND: Major histocompatibility complex class I chain-related (MIC) A and B (MICA and MICB) are polymorphic stress molecules recognized by natural killer cells. This study was performed to analyze MIC gene profiles in hospitalized Thai children with acute dengue illness. METHODS: MIC allele profiles were determined in a discovery cohort of patients with dengue fever or dengue hemorrhagic fever (DHF) (n = 166) and controls (n = 149). A replication cohort of patients with dengue (n = 222) was used to confirm specific MICB associations with disease. RESULTS: MICA*045 and MICB*004 associated with susceptibility to DHF in secondary dengue virus (DENV) infections (odds ratio [OR], 3.22; [95% confidence interval (CI), 1.18-8.84] and 1.99 [1.07-2.13], respectively), and MICB*002 with protection from DHF in secondary DENV infections (OR, 0.41; 95% CI, .21-.68). The protective effect of MICB*002 against secondary DHF was confirmed in the replication cohort (OR, 0.43; 95% CI, .22-.82) and was stronger when MICB*002 is present in individuals also carrying HLA-B*18, B*40, and B*44 alleles which form the B44 supertype of functionally related alleles (0.29, 95% CI, .14-.60). CONCLUSIONS: Given that MICB*002 is a low expresser of soluble proteins, these data indicate that surface expression of MICB*002 with B44 supertype alleles on DENV-infected cells confer a protective advantage in controlling DENV infection using natural killer cells.

Asunto(s)

Pueblo Asiatico/genética , Genes MHC Clase I/genética , Predisposición Genética a la Enfermedad , Antígenos de Histocompatibilidad Clase I/genética , Dengue Grave/genética , Adolescente , Alelos , Niño , Preescolar , Antígeno HLA-B18/genética , Antígeno HLA-B40/genética , Antígeno HLA-B44/genética , Haplotipos , Humanos , Desequilibrio de Ligamiento/genética , Factores Protectores , Tailandia/etnología

RESUMEN

Novel allele HLA-B*56:67 potentially formed by recombination between B*56:01:01:03 and B*40:01:01.

Asunto(s)

Antígenos HLA-B/genética , Antígeno HLA-B40/genética , Alelos , Exones , Humanos , Intrones , Nueva Caledonia/etnología , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN

RESUMEN

One nucleotide substitution in codon 140 of HLA-B*40:01:01 results in a novel allele, HLA-B*40:62.

Asunto(s)

Alelos , Codón , Antígeno HLA-B40/genética , Células Madre Hematopoyéticas , Donantes de Tejidos , Pueblo Asiatico , Humanos , Taiwán

RESUMEN

HLA-B*40:01:43 was initially identified in a volunteer donor for China marrow donor program by sequence-based typing.

Asunto(s)

Alelos , Antígeno HLA-B40/genética , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Pueblo Asiatico , Humanos

RESUMEN

HLA-B*40:357 shows a substitution C to G at position 263 when compared to HLA-B*40:01:01.

Asunto(s)

Antígeno HLA-B40/genética , Prueba de Histocompatibilidad/métodos , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN/métodos , Alelos , Sustitución de Aminoácidos , Pueblo Asiatico/genética , Secuencia de Bases , Humanos , Homología de Secuencia , Donantes de Tejidos

RESUMEN

Genomic full-length sequence of HLA-B*40:54 was identified by a group-specific sequencing approach from China.

Asunto(s)

Antígeno HLA-B40/genética , Regiones no Traducidas 3' , Regiones no Traducidas 5' , Alelos , Pueblo Asiatico , Secuencia de Bases , China/etnología , Exones , Humanos , Intrones , Análisis de Secuencia de ADN

RESUMEN

One nucleotide substitution at residue 865 of HLA-B*40:01:01 results in a novel allele, HLA-B*40:221.

Asunto(s)

Antígeno HLA-B40/genética , Alelos , Arginina/química , Bases de Datos Factuales , Exones , Genotipo , Glicina/química , Prueba de Histocompatibilidad , Humanos , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Taiwán

RESUMEN

The new allele, HLA-B*40:405 differs from B*40:02:01:01 by one nucleotide substitution at codon 304.

Asunto(s)

Alelos , Antígeno HLA-B40/genética , Síndromes Mielodisplásicos/genética , Adulto , Codón , Exones , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , República de Corea

RESUMEN

Identification of the novel allele HLA-B*40:379 carrying polymorphisms in an intron, exon and the 3' untranslated region.

Asunto(s)

Alelos , Antígeno HLA-B40/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Regiones no Traducidas 3'/genética , Secuencia de Bases , Exones/genética , Humanos

RESUMEN

Genetic investigations on ancient human remains affected by rheumatological pathologies are a research field of particular interest for identifying the pathogenesis of diseases, especially those having an autoimmune background such as spondyloarthopaties (SpA). Reliable studies concerning this topic require collaboration between multiple disciplines, usually starting from paleopathologic observations up to molecular genetic screening. Here, we focused our investigation in a medieval necropolis in the Basque Country (13th-15th century, N = 163), which presents a high frequency of joint pathologies through two approaches: on the one hand, the analysis of joint manifestations for the differential diagnosis of the SpA and, on the other hand, the determination of the alleles of the HLA-B gene. The morphological analysis allowed determining that 30% of the individuals had rheumatic bone manifestations, with SpA being the most frequent (45%). The genetic analysis of individuals with and without pathologies, based on the study of the HLA-B gene, allowed finding 17 alleles for this gene, with HLA-B40, HLA-B27 and HLA-B35 being the most frequent. Although these alleles have been traditionally described as genetic markers associated to the development of SpA, in this study they were also found in individuals with other rheumatic diseases (osteoarthritis and rheumatoid arthritis) and even in individuals without pathologies. These data confirm the complexity of the relationship of the HLA-B gene variants with SpA, since it is not possible to establish a diagnosis of SpA with these variants alone. However, we suggest that allele HLA-B40, in combination with some specific rheumatic bone manifestations, facilitates the diagnosis of SpA.

Asunto(s)

Artritis Reumatoide/diagnóstico , Antígeno HLA-B27/genética , Antígeno HLA-B35/genética , Antígeno HLA-B40/genética , Osteoartritis/diagnóstico , Polimorfismo Genético , Espondiloartropatías/diagnóstico , Alelos , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Restos Mortales , Huesos/inmunología , Huesos/patología , Clima , Frío , ADN Antiguo/análisis , Diagnóstico Diferencial , Femenino , Predisposición Genética a la Enfermedad , Antígeno HLA-B27/inmunología , Antígeno HLA-B35/inmunología , Antígeno HLA-B40/inmunología , Historia Medieval , Humanos , Articulaciones/inmunología , Articulaciones/patología , Masculino , Osteoartritis/genética , Osteoartritis/inmunología , Osteoartritis/patología , Paleopatología/métodos , España , Espondiloartropatías/genética , Espondiloartropatías/inmunología , Espondiloartropatías/patología

RESUMEN

B*40:302 differs from B*40:02:01:01 by a single nonsynonymous nucleotide substitution at codon 81 (CCG→CTG).

Asunto(s)

Alelos , Exones , Antígeno HLA-B40/genética , Polimorfismo de Nucleótido Simple , Sustitución de Aminoácidos , Pueblo Asiatico , Secuencia de Bases , Codón/química , Expresión Génica , Genotipo , Antígeno HLA-B40/inmunología , Prueba de Histocompatibilidad , Humanos , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADN

RESUMEN

The HLA-B*40:238 allele has one non-synonymous transversion from HLA-B*40:01:01 at nucleotide position 484.

Asunto(s)

Alelos , Exones , Enfermedad de Graves/genética , Antígeno HLA-B40/genética , Polimorfismo de Nucleótido Simple , Sustitución de Aminoácidos , Secuencia de Bases , Codón/química , Expresión Génica , Genotipo , Enfermedad de Graves/inmunología , Enfermedad de Graves/patología , Antígeno HLA-B40/inmunología , Prueba de Histocompatibilidad , Humanos , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADN , Taiwán

RESUMEN

HLA-B*40:01:41 differs from HLA-B*40:01:01 by a single nucleotide substitution at position 195 G>A.

Asunto(s)

Alelos , Técnicas de Genotipaje , Antígeno HLA-B40/genética , Reacción en Cadena de la Polimerasa , Pueblo Asiatico , Donantes de Sangre , Sangre Fetal , Humanos