The novel HLA-A*02:1140 allele, first described in a potential bone marrow donor from Brazil.
Alleles , HLA-A2 Antigen , Humans , Brazil , HLA-A2 Antigen/genetics , HLA-A2 Antigen/immunology , Histocompatibility Testing , Exons , Tissue Donors , Base Sequence , Sequence Analysis, DNA/methods , Sequence Alignment
Introduction: Polymorphisms in the KIR and HLA genes contribute to the diversity of the NK cell repertoire. Extrinsic factors also play a role in modifying this repertoire. The best example is cytomegalovirus, which promotes the expansion of memory-like NK cells. However, the mechanisms governing this phenotypic structure are poorly understood. Furthermore, the influence of age and sex has been understudied. Methods: In this study, we examined these parameters in a cohort of 200 healthy volunteer blood donors, focusing on the major inhibitory KIR receptors and CD94/NKG2A, as well as the differentiation marker CD57 and the memory-like population marker NKG2C. Flow cytometry and two joint analyses, unsupervised and semi-supervised, helped define the impact of various intrinsic and extrinsic markers on the phenotypic structure of the NK cell repertoire. Results: In the KIR NK cell compartment, the KIR3DL1 gene is crucial, as unexpressed alleles lead to a repertoire dominated by KIR2D interacting only with HLA-C ligands, whereas an expressed KIR3DL1 gene allows for a greater diversity of NK cell subpopulations interacting with all HLA class I ligands. KIR2DL2 subsequently favors the KIR2D NK cell repertoire specific to C1/C2 ligands, whereas its absence promotes the expression of KIR2DL1 specific to the C2 ligand. The C2C2Bw4+ environment, marked by strong -21T motifs, favors the expansion of the NK cell population expressing only CD57, whereas the absence of HLA-A3/A11 ligands favors the population expressing only NKG2A, a population highly represented within the repertoire. The AA KIR genotype favors NK cell populations without KIR and NKG2A receptors, whereas the KIR B+ genotypes favor populations expressing KIR and NKG2A. Interestingly, we showed that women have a repertoire enriched in CD57- NK cell populations, while men have more CD57+ NK cell subpopulations. Discussion: Overall, our data demonstrate that the phenotypic structure of the NK cell repertoire follows well-defined genetic rules and that immunological history, sex, and age contribute to shaping this NK cell diversity. These elements can contribute to the better selection of hematopoietic stem cell donors and the definition of allogeneic NK cells for cell engineering in NK cell-based immunotherapy approaches.cters are displayed correctly.
Cytomegalovirus Infections , Cytomegalovirus , Genotype , Killer Cells, Natural , Receptors, KIR , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Female , Male , Adult , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/genetics , Cytomegalovirus/immunology , Receptors, KIR/genetics , Middle Aged , Sex Factors , Age Factors , CD57 Antigens , Histocompatibility Testing , Young Adult , NK Cell Lectin-Like Receptor Subfamily C/genetics , HLA Antigens/genetics , HLA Antigens/immunology , Aged , Receptors, KIR3DL1/genetics
The novel HLA-C*08:275 allele, first described in a potential bone marrow donor from Brazil.
Alleles , Exons , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Brazil , Histocompatibility Testing , Tissue Donors , Base Sequence , Sequence Analysis, DNA/methods , Sequence Alignment , Codon
Nucleotide substitution in codon 238 of HLA-C*12:02:02:01 results in a novel allele, HLA-C*12:02:53.
Alleles , Base Sequence , Codon , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Taiwan , Sequence Analysis, DNA , Asian People/genetics , Sequence Alignment , Polymorphism, Single Nucleotide , Amino Acid Substitution
Five novel HLA-C alleles detected by next-generation sequencing: HLA-C*02:02:73, -C*03:04:106, -C*06:382, -C*07:1114Q and -C*12:408.
Alleles , HLA-C Antigens , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Humans , High-Throughput Nucleotide Sequencing/methods , HLA-C Antigens/genetics , Histocompatibility Testing/methods , Exons , Sequence Analysis, DNA/methods
The novel HLA-B*35:593 allele, first described in a potential bone marrow donor from Brazil.
Alleles , Exons , Humans , Histocompatibility Testing/methods , Sequence Analysis, DNA/methods , Tissue Donors , Brazil , HLA-B35 Antigen/genetics , HLA-B Antigens/genetics , High-Throughput Nucleotide Sequencing/methods , Base Sequence
Compared with HLA-DRB1*12:02, the alleles HLA-DRB1*12:92 and HLA-DRB1*12:101 each show one nucleotide substitution respectively.
Alleles , HLA-DRB1 Chains , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Humans , HLA-DRB1 Chains/genetics , High-Throughput Nucleotide Sequencing/methods , Histocompatibility Testing/methods , Exons , Polymorphism, Single Nucleotide , Base Sequence , Sequence Analysis, DNA/methods
HLA-DQA1*02:32 differs from DQA1*02:01:01 by one nucleotide substitution in codon 210 in exon 4.
Alleles , Exons , HLA-DQ alpha-Chains , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Humans , HLA-DQ alpha-Chains/genetics , High-Throughput Nucleotide Sequencing/methods , Histocompatibility Testing/methods , Base Sequence , Codon , Sequence Analysis, DNA/methods
The novel HLA-C*15:274 allele, first described in a potential bone marrow donor from Brazil.
Alleles , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Histocompatibility Testing/methods , Sequence Analysis, DNA/methods , Tissue Donors , Brazil , High-Throughput Nucleotide Sequencing/methods , Base Sequence
Two different single nucleotide substitutions in intron 2 give rise to novel HLA-DQB1*03:02:01 alleles.
Alleles , HLA-DQ beta-Chains , Introns , Humans , Histocompatibility Testing , HLA-DQ beta-Chains/genetics , Polymorphism, Single Nucleotide
The novel HLA-DPA1*02:07:04 allele was detected during the HLA typing for kidney transplantation.
Alleles , HLA-DP alpha-Chains , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Kidney Transplantation , Humans , HLA-DP alpha-Chains/genetics , High-Throughput Nucleotide Sequencing/methods , Histocompatibility Testing/methods , Exons
HLA-B*15:02:15 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.
Exons , HLA-B15 Antigen , Histocompatibility Testing , Humans , Alleles , Base Sequence , Codon , East Asian People , HLA-B15 Antigen/genetics , HLA-B15 Antigen/immunology , Sequence Alignment , Sequence Analysis, DNA/methods
HLA-C*03:620 differs from the HLA-C*03:04:01:02 allele by one nucleotide substitution in the exon 3.
Alleles , Asian People , Base Sequence , Exons , HLA-C Antigens , Histocompatibility Testing , Humans , HLA-C Antigens/genetics , Asian People/genetics , Sequence Analysis, DNA/methods , Codon , Sequence Alignment , Polymorphism, Single Nucleotide , East Asian People
HLA-DPB1*05:01:20 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.
Alleles , Asian People , Base Sequence , Exons , HLA-DP beta-Chains , Histocompatibility Testing , Sequence Analysis, DNA , Humans , HLA-DP beta-Chains/genetics , Asian People/genetics , Sequence Analysis, DNA/methods , Tissue Donors , Sequence Alignment , Codon , East Asian People
HLA-B*15:659 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.
Alleles , Asian People , Base Sequence , Exons , Histocompatibility Testing , Sequence Analysis, DNA , Humans , Asian People/genetics , Sequence Analysis, DNA/methods , HLA-B15 Antigen/genetics , HLA-B15 Antigen/immunology , Sequence Alignment , Codon , Tissue Donors , East Asian People
Genomic full-length sequence of HLA-B*37:46 was identified by a group-specific sequencing approach in a Chinese individual.
Alleles , Asian People , HLA-B Antigens , Histocompatibility Testing , Sequence Analysis, DNA , Humans , HLA-B Antigens/genetics , Sequence Analysis, DNA/methods , Histocompatibility Testing/methods , Asian People/genetics , Exons , Base Sequence
HLA-DQB1*06:466 differs from HLA-DQB1*06:01:01:01 by a single nucleotide substitution at position 571GâA.
Alleles , Asian People , Blood Donors , Exons , Fetal Blood , HLA-DQ beta-Chains , High-Throughput Nucleotide Sequencing , Humans , HLA-DQ beta-Chains/genetics , High-Throughput Nucleotide Sequencing/methods , Asian People/genetics , Histocompatibility Testing/methods , Polymorphism, Single Nucleotide , Base Sequence , Sequence Analysis, DNA/methods , East Asian People
HLA-A*01:454 and HLA-A*31:229, two novel HLA-A alleles detected during routine typing by next-generation sequencing.
Alleles , Exons , HLA-A Antigens , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , Humans , HLA-A Antigens/genetics , Sequence Analysis, DNA/methods , HLA-A1 Antigen/genetics , Base Sequence
HLA-DRB4*01:01:12 differs from HLA-DRB4*01:01:01:01 by one nucleotide substitution in codon 175 in exon 3.
Alleles , Base Sequence , Exons , HLA-DRB4 Chains , Histocompatibility Testing , Sequence Analysis, DNA , Humans , Histocompatibility Testing/methods , Sequence Analysis, DNA/methods , HLA-DRB4 Chains/genetics , Codon , Sequence Alignment
Assessing donor/recipient HLA compatibility at the eplet level requires second field DNA typings but these are not always available. These can be estimated from lower-resolution data either manually or with computational tools currently relying, at best, on data containing typing ambiguities. We gathered NGS typing data from 61,393 individuals in 17 French laboratories, for loci A, B, and C (100% of typings), DRB1 and DQB1 (95.5%), DQA1 (39.6%), DRB3/4/5, DPB1, and DPA1 (10.5%). We developed HaploSFHI, a modified iterative maximum likelihood algorithm, to impute second field HLA typings from low- or intermediate-resolution ones. Compared with the reference tools HaploStats, HLA-EMMA, and HLA-Upgrade, HaploSFHI provided more accurate predictions across all loci on two French test sets and four European-independent test sets. Only HaploSFHI could impute DQA1, and solely HaploSFHI and HaploStats provided DRB3/4/5 imputations. The improved performance of HaploSFHI was due to our local and nonambiguous data. We provided explanations for the most common imputation errors and pinpointed the variability of a low number of low-resolution haplotypes. We thus provided guidance to select individuals for whom sequencing would optimize incompatibility assessment and cost-effectiveness of HLA typing, considering not only well-imputed second field typing(s) but also well-imputed eplets.
High-Throughput Nucleotide Sequencing , Tissue Donors , Humans , Alleles , Haplotypes , Histocompatibility Testing , HLA Antigens/genetics , Gene Frequency