ABSTRACT
HLA-B*40:86 differs from B*40:06:01:03 by a single nucleotide exchange in exon 3.
Subject(s)
Exons , HLA-B40 Antigen , Humans , Alleles , Base Sequence , East Asian People/genetics , Histocompatibility Testing , HLA-B40 Antigen/genetics , Polymorphism, Single Nucleotide , Sequence Analysis, DNA/methodsABSTRACT
One nucleotide substitution in codon 81 of HLA-B*40:01:01 results in a novel allele, HLA-B*40:400.
Subject(s)
Alleles , Exons , HLA-B40 Antigen , Haplotypes , Histocompatibility Testing , Humans , Taiwan , HLA-B40 Antigen/genetics , Base Sequence , Codon , Sequence Analysis, DNA/methods , Asian People/genetics , Polymorphism, Single Nucleotide , Sequence Alignment , HLA-B Antigens/geneticsABSTRACT
HLA-B*40:550 differs from HLA-B*40:01:02:01 by one nucleotide in exon 1.
Subject(s)
Exons , HLA-B40 Antigen , Histocompatibility Testing , Humans , Alleles , Base Sequence , Codon , East Asian People , HLA-B40 Antigen/genetics , Sequence Alignment , Sequence Analysis, DNA/methodsABSTRACT
Identification of two novel HLA alleles in Russian bone marrow donors.
Subject(s)
Alleles , Tissue Donors , Humans , Russia , HLA-A2 Antigen/genetics , HLA-A2 Antigen/immunology , Bone Marrow Transplantation , HLA-B40 Antigen/genetics , HLA-B40 Antigen/immunology , Exons , Histocompatibility Testing , Bone Marrow , Sequence Analysis, DNAABSTRACT
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.
Subject(s)
Carcinoma, Adenosquamous , Oncogene Proteins, Viral , Papillomavirus Infections , Vaccines, DNA , Animals , Aspartic Acid , CD8-Positive T-Lymphocytes , Carcinoma, Adenosquamous/complications , Epitopes, T-Lymphocyte/genetics , Female , HLA-A Antigens , HLA-A1 Antigen , HLA-A11 Antigen , HLA-A2 Antigen/genetics , HLA-A24 Antigen , HLA-B40 Antigen , HLA-B44 Antigen , HLA-B7 Antigen , HeLa Cells , Human papillomavirus 18 , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oncogene Proteins, Viral/genetics , Papillomavirus Infections/complications , Peptides , Proto-Oncogene Proteins c-akt , T-Lymphocytes, Cytotoxic , Vaccines, DNA/geneticsABSTRACT
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) (nâ =â 166) and controls (nâ =â 149). A replication cohort of patients with dengue (nâ =â 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],â 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,â 0.41; 95% CI, .21-.68). The protective effect of MICB*002 against secondary DHF was confirmed in the replication cohort (OR,â 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.
Subject(s)
Asian People/genetics , Genes, MHC Class I/genetics , Genetic Predisposition to Disease , Histocompatibility Antigens Class I/genetics , Severe Dengue/genetics , Adolescent , Alleles , Child , Child, Preschool , HLA-B18 Antigen/genetics , HLA-B40 Antigen/genetics , HLA-B44 Antigen/genetics , Haplotypes , Humans , Linkage Disequilibrium/genetics , Protective Factors , Thailand/ethnologyABSTRACT
Novel allele HLA-B*56:67 potentially formed by recombination between B*56:01:01:03 and B*40:01:01.
Subject(s)
HLA-B Antigens/genetics , HLA-B40 Antigen/genetics , Alleles , Exons , Humans , Introns , New Caledonia/ethnology , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Sequence Analysis, DNAABSTRACT
HLA-B*40:01:43 was initially identified in a volunteer donor for China marrow donor program by sequence-based typing.
Subject(s)
Alleles , HLA-B40 Antigen/genetics , Histocompatibility Testing , Sequence Analysis, DNA , Asian People , HumansABSTRACT
One nucleotide substitution in codon 140 of HLA-B*40:01:01 results in a novel allele, HLA-B*40:62.
Subject(s)
Alleles , Codon , HLA-B40 Antigen/genetics , Hematopoietic Stem Cells , Tissue Donors , Asian People , Humans , TaiwanABSTRACT
HLA-B*40:357 shows a substitution C to G at position 263 when compared to HLA-B*40:01:01.
Subject(s)
HLA-B40 Antigen/genetics , Histocompatibility Testing/methods , Polymerase Chain Reaction/methods , Polymorphism, Single Nucleotide , Sequence Analysis, DNA/methods , Alleles , Amino Acid Substitution , Asian People/genetics , Base Sequence , Humans , Sequence Homology , Tissue DonorsABSTRACT
The new allele, HLA-B*40:405 differs from B*40:02:01:01 by one nucleotide substitution at codon 304.
Subject(s)
Alleles , HLA-B40 Antigen/genetics , Myelodysplastic Syndromes/genetics , Adult , Codon , Exons , Female , High-Throughput Nucleotide Sequencing , Humans , Republic of KoreaABSTRACT
One nucleotide substitution at residue 865 of HLA-B*40:01:01 results in a novel allele, HLA-B*40:221.
Subject(s)
HLA-B40 Antigen/genetics , Alleles , Arginine/chemistry , Databases, Factual , Exons , Genotype , Glycine/chemistry , Histocompatibility Testing , Humans , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , TaiwanABSTRACT
Genomic full-length sequence of HLA-B*40:54 was identified by a group-specific sequencing approach from China.
Subject(s)
HLA-B40 Antigen/genetics , 3' Untranslated Regions , 5' Untranslated Regions , Alleles , Asian People , Base Sequence , China/ethnology , Exons , Humans , Introns , Sequence Analysis, DNAABSTRACT
Identification of the novel allele HLA-B*40:379 carrying polymorphisms in an intron, exon and the 3' untranslated region.
Subject(s)
Alleles , HLA-B40 Antigen/genetics , High-Throughput Nucleotide Sequencing , 3' Untranslated Regions/genetics , Base Sequence , Exons/genetics , HumansABSTRACT
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, Nâ¯=â¯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.
Subject(s)
Arthritis, Rheumatoid/diagnosis , HLA-B27 Antigen/genetics , HLA-B35 Antigen/genetics , HLA-B40 Antigen/genetics , Osteoarthritis/diagnosis , Polymorphism, Genetic , Spondylarthropathies/diagnosis , Alleles , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Body Remains , Bone and Bones/immunology , Bone and Bones/pathology , Climate , Cold Temperature , DNA, Ancient/analysis , Diagnosis, Differential , Female , Genetic Predisposition to Disease , HLA-B27 Antigen/immunology , HLA-B35 Antigen/immunology , HLA-B40 Antigen/immunology , History, Medieval , Humans , Joints/immunology , Joints/pathology , Male , Osteoarthritis/genetics , Osteoarthritis/immunology , Osteoarthritis/pathology , Paleopathology/methods , Spain , Spondylarthropathies/genetics , Spondylarthropathies/immunology , Spondylarthropathies/pathologyABSTRACT
B*40:302 differs from B*40:02:01:01 by a single nonsynonymous nucleotide substitution at codon 81 (CCGâCTG).
Subject(s)
Alleles , Exons , HLA-B40 Antigen/genetics , Polymorphism, Single Nucleotide , Amino Acid Substitution , Asian People , Base Sequence , Codon/chemistry , Gene Expression , Genotype , HLA-B40 Antigen/immunology , Histocompatibility Testing , Humans , Polymerase Chain Reaction , Sequence Alignment , Sequence Analysis, DNAABSTRACT
The HLA-B*40:238 allele has one non-synonymous transversion from HLA-B*40:01:01 at nucleotide position 484.
Subject(s)
Alleles , Exons , Graves Disease/genetics , HLA-B40 Antigen/genetics , Polymorphism, Single Nucleotide , Amino Acid Substitution , Base Sequence , Codon/chemistry , Gene Expression , Genotype , Graves Disease/immunology , Graves Disease/pathology , HLA-B40 Antigen/immunology , Histocompatibility Testing , Humans , Polymerase Chain Reaction , Sequence Alignment , Sequence Analysis, DNA , TaiwanABSTRACT
HLA-B*40:01:41 differs from HLA-B*40:01:01 by a single nucleotide substitution at position 195 G>A.
Subject(s)
Alleles , Genotyping Techniques , HLA-B40 Antigen/genetics , Polymerase Chain Reaction , Asian People , Blood Donors , Fetal Blood , HumansABSTRACT
A one nucleotide replacement in codon 261 of HLA-B*40:01:01 results in a novel allele, HLA-B*40:247.
Subject(s)
Genotyping Techniques , HLA-B40 Antigen/genetics , Sequence Analysis, DNA , Asian People , Humans , TaiwanABSTRACT
The HLA-B*40:242 allele differs from B*40:54 by 1 nucleotide substitution at position 190.