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1.
Int J Immunogenet ; 44(5): 225-233, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28691368

RESUMO

The split specificities of HLA-B14 (B64, B65) are assigned to the B*14:01 (B64) and B*14:02 (B65) products only. Of the further 50 B*14 expressed products, only B*14:03 and B*14:06 are officially designated as HLA-B14. The B*14:08 product differs from B64 by a single amino acid substitution of W97R, while the B*14:53 specificity (which is a "short" B14 and neither B64 nor B65) differs from B64 by three residues (W97S, Y113H and F116Y). Comprehensive testing of B*14:08:01 cells (using 49 alloantisera with B64 or B64, B65 specificities, and five monoclonal antibodies with B65 or B64, B65 activity) showed that the B*14:08 specificity is, like the B*14:53 product, neither B64 nor B65 and appears as a "short" B14 specificity. To help understand the serological reactivity of the B*14:08 and B*14:53 products, and B64 and B65, we identified seven published epitopes (11AV, 97W, 61ICT, 116F, 131S+163T, 170RH and 420) and, by inspection, 29 motifs, that encompass one or more of B64, B65 and various HLA-B14 cross-reactive group specificities. We then considered the possession of these epitopes and motifs by the products of B*14:01 to B*14:06, B*14:08 and B*14:53. Seventeen of the 29 motifs fully complied with the one-/two-patch functional epitope concept for amino acid proximity, as determined by Cn3D software, the remainder partially complied. The nature and patterns of epitopes and motifs possessed by both B*14:08 and B*14:53 specificities supported their designation as HLA-B14 but non-B64/B65. Also that epitope 97W, with 11S or 11A, is critical for serological B64 and B65 reactivity. And conversely, that epitope 116F, and several identified motifs, are probably unimportant for HLA-B14 antibody reactivity. The previous submission that the B*14:03 specificity is HLA-B65 was compatible with its epitope/motif pattern. B*14:04 cells would also be expected to react as B65, based on its epitope/motif pattern, and not as B64 as previously implied. Also, from their epitope/motif patterns, and external serological information, it is probable that the B*14:05 and B*14:06 specificities will both appear as "short" HLA-B14, non-B64/B65. Several epitopes and motifs encompassed a range of HLA-B specificities included in the serological HLA-B14 cross-reactive group, thus supporting these original serological findings.


Assuntos
Substituição de Aminoácidos/genética , Epitopos/imunologia , Antígeno HLA-B14/imunologia , Isoanticorpos/imunologia , Alelos , Motivos de Aminoácidos/genética , Motivos de Aminoácidos/imunologia , Substituição de Aminoácidos/imunologia , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos/imunologia , Reações Cruzadas/imunologia , Epitopos/genética , Antígeno HLA-B14/genética , Humanos , Isoanticorpos/genética
2.
Int J Immunogenet ; 44(4): 169-170, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28639429

RESUMO

The sequencing of exons 2-7 of a likely new HLA-C*05 allele identified the second example of HLA-C*05:142, in a male UK European, within a few months of the first example being found in Germany. C*05:142 differs from C*05:01:01:01 by a single base (395G>C) in exon 3 resulting in an amino acid substitution of R108P. Comprehensive serological HLA-Cw5 typing, using 19 antisera, indicated that C*05:142 encodes a "normal" Cw5 specificity. Failure to identify the involvement of position 108 in published HLA-C epitopes supported this assertion. The likely HLA class I C*05:142-bearing haplotype is A*02:01~C*05:142~B*44:02. This new allele has a maximum frequency of 0.00001, in 34,743 sequenced-based typed subjects, contrasting with that of C*05:01 (allele frequency 0.10441), in our local, largely UK European, blood donors.


Assuntos
Alelos , Epitopos/genética , Éxons , Frequência do Gene , Antígenos HLA-C/genética , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Humanos , Reino Unido
3.
Int J Immunogenet ; 43(4): 236-9, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27312672

RESUMO

HLA-B*14:53 was found in a UK European normal blood donor prior to registration on the Welsh Bone Marrow Donor Registry. It differs from B*14:13 by one base (103G>T) in exon 2 resulting in a substitution of alanine (A) in B*14:13 to serine (S) in B*14:53. Unique among current HLA-B*14 alleles, B*14:53 and B*14:13 share a motif of 59 bases between positions 361 and 419 in exon 3. This motif is present in numerous HLA-B alleles the commonest overall being B*08:01, suggesting that both B*14:53 and B*14:13 arose from intralocus gene conversion events with B*08:01. Thus, B*14:53 probably arose from B*14:01:01 (which has TCC at codon 11 (S), while B*14:13 arose from B*14:02:01:01 which has GCC at codon 11 (A). Additionally, the two likely B*14:53-bearing and B*14:13-bearing haplotypes are typical of B*14:01:01-bearing and B*14:02:01:01-bearing haplotypes, respectively. Serological testing, using 49 antisera with HLA-B64, or B64, B65 reactivity, showed that the B*14:53 specificity did not react as a B64 (B*14:01) specificity and may appear as a short/weak HLA-B14. This implies that residues additional to S at position 11 are involved in HLA-B64 serological identity; for example, the motif 11S 97W 116F is possessed by B*14:01 and many other B*14 products (and B*39:79 plus some HLA-C products) but not B65 (B*14:02) or the B*14:53 specificity. B*14:53 was found in a random HLA sequence-based typed population of 32 530 normal subjects indicating a low precision allele frequency of 0.000015 in subjects resident in Wales.


Assuntos
Antígenos HLA-B/genética , Antígenos HLA-C/genética , Alelos , Doadores de Sangue , Éxons , Frequência do Gene , Antígenos HLA-B/imunologia , Antígenos HLA-C/imunologia , Haplótipos , Humanos , País de Gales
4.
Int J Immunogenet ; 43(1): 40-4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26684212

RESUMO

Three novel HLA-Class II alleles, DRB1*03:112, DQB1*03:02:16 and DQB1*03:139, are described with predicted bearing haplotypes of A*02:01, B*40:01, C*03:04, DRB1*03:112, DQB1*02:01; A*23:01, B*15:01, C*03:03, DRB1*04:01, DQB1*03:02:16 and A*01:01, B*44:02, C*05:01/03, DRB1*04:01, DQB1*03:139. Serological tests showed that the DRB1*03:112 and DQB1*03:139 specificities failed to react as expected with some well-documented monoclonal antibodies. Subsequent examination of published HLA-Class II epitopes and inspection of amino acid motifs suggested that epitopes exist that include the positions of their single substitutions (F31C between DRB1*03:01:01:01 and DRB1*03:112, and R48P between DQB1*03:01:01:01 and DQB1*03:139 specificities). This suggests that the reactivity of the monoclonal antibodies used was dependent on these epitopes and that their loss from these rare allele products resulted in their aberrant serology. The new alleles were found after the sequence-based typing of 32 530 random UK European routine blood donors suggesting that each has a maximum carriage frequency of 0.0031% in the blood donor population resident in Wales.


Assuntos
Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Imunogenética , Alelos , Doadores de Sangue , Genética Populacional , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/imunologia , Haplótipos/genética , Haplótipos/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Humanos , País de Gales
5.
Tissue Antigens ; 86(3): 216-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26206472

RESUMO

Three novel HLA-DQB1 alleles were found after sequence-based typing of 3558 random UK European routine blood donors.


Assuntos
Alelos , Cadeias beta de HLA-DQ/genética , Humanos
6.
Tissue Antigens ; 85(6): 506-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25757845

RESUMO

HLA-A*26:103 differs from A*26:01:01 by one base (559C>G) in exon 3 resulting in an amino acid substitution of R163G.


Assuntos
Genes MHC Classe I , Antígenos HLA-A/genética , Alelos , Motivos de Aminoácidos , Sequência de Bases , Medula Óssea , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Doadores de Tecidos , País de Gales
7.
Int J Immunogenet ; 42(1): 15-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25545392

RESUMO

An HLA-DQA1 sequence-based typing method reliant upon group-specific amplification to achieve an unambiguous second-field DQA1 typing assignment is presented. Method validation, using 51 reference DNA samples covering 21 different DQA1 alleles, showed 100% concordance with the reference types. This typing strategy has several important uses including identifying DQA1 mismatches in kidney donor/recipient pairs to inform patient DQ antibody assignments.


Assuntos
Cadeias alfa de HLA-DQ/genética , Cadeias alfa de HLA-DQ/imunologia , Teste de Histocompatibilidade/métodos , Sequência de Bases , Humanos , Transplante de Rim , Reação em Cadeia da Polimerase , Polimorfismo Genético , Análise de Sequência de DNA
11.
Int J Immunogenet ; 41(4): 277-80, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24762294

RESUMO

Hypersensitivity reactions to the drug abacavir are strongly associated with possession of HLA-B*57:01. Hence, patients with HIV/AIDS who may be prescribed abacavir should be tested for this HLA allele and the drug withheld from those that possess B*57:01. The UK National External Quality Assessment Service for Histocompatibility and Immunogenetics has operated a scheme for B*57:01 testing since 2008 which, in 2013, involved 47 participants from 12 countries. A total of 24 B*57:01-positive, 2 B*57:03-positive and 22 B*57-negative blood samples (including 2 B*58 samples) were distributed to between 28 and 47 laboratories each year over 6 years. Participants, who were unaware of the samples' HLA types, tested and reported on their B*57/B*57:01 status. A total of 1868 reports were assessed over the 6 years. Of the 880 reports on B*57:01 samples, 93.4% were correctly assigned as B*57:01, 2.8% were assigned as groups of B*57 alleles including B*57:01, and 3.3% were reported as B*57 positive only. Over the 6 years, there were four (0.46%) false B*57:01 negative reports. All the B*57:03-positive and B*57-negative samples, involving 72 and 916 assignments, respectively, were essentially reported as B*57:01 negative. Thus, there were no false B57:01 positive assignments. The reporting of B*57:01 status over the last 3 years of the scheme was 99.8% sensitive and 100% specific. Over the last year, it was 100% sensitive and 100% specific.


Assuntos
Didesoxinucleosídeos/imunologia , Hipersensibilidade a Drogas/imunologia , Antígenos HLA-B/imunologia , Teste de Histocompatibilidade/estatística & dados numéricos , Alelos , Fármacos Anti-HIV/imunologia , Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/genética , Testes Genéticos/métodos , Testes Genéticos/normas , Testes Genéticos/estatística & dados numéricos , Antígenos HLA-B/genética , Teste de Histocompatibilidade/métodos , Teste de Histocompatibilidade/normas , Humanos , Reação em Cadeia da Polimerase , Controle de Qualidade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Int J Immunogenet ; 41(6): 480-3, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25345618

RESUMO

Two hundred and fifty-four normal blood donors, from a largely UK European population, were sequence-based typed for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1 and HLA-DQB1. The fit to Hardy-Weinberg expectations was good for all loci (all P values >0.5). Fifteen DQA1 alleles were identified to the second field. DQA1 carriage, allele and DQA1-DQB1 and DRB1-DQA1-DQB1 haplotype frequencies, linkage disequilibria and related values are presented.


Assuntos
Alelos , Doadores de Sangue , Cadeias alfa de HLA-DQ/genética , Haplótipos/genética , Características de Residência , Frequência do Gene , Humanos , Prevalência , País de Gales
13.
Int J Immunogenet ; 40(4): 311-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23280011

RESUMO

Hypersensitivity reactions to the drug abacavir, used to treat HIV/AIDS patients, is associated with possession of HLA-B*57:01. We have carefully assessed two commercially available HLA-B57/B58 murine monoclonal antibodies [0196HA and BIH0243 (One Lambda Inc.)] in a simple flow cytometry-based assay. The evaluation involved tests on 228 reference and random samples covering 91% of all WHO recognized HLA-A, B and C specificities. These involved donors with six different HLA-B*57 alleles and included 19 examples of B*57:01. Both antibodies unambiguously detected B57, but there were small difference in their reactivity against B57-positive non-B*57:01 samples. Importantly, there was no reactivity against B57/B58-negative samples. The possible amino acid motifs involved in the reactivity of these antibodies with B57/B58 were delineated. Thus, HLA-B57/B58, normally present in <10% of patients, can be easily recognized using these two antibodies and further tested by a DNA-based typing method to identify B*57:01.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Anticorpos Monoclonais/imunologia , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Antígenos HLA-B/análise , Alelos , Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/genética , Hipersensibilidade a Drogas/imunologia , Prescrições de Medicamentos , Epitopos/genética , Citometria de Fluxo , Variação Genética , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Humanos
14.
Int J Immunogenet ; 40(1): 21-30, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23280239

RESUMO

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.


Assuntos
Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Cadeias HLA-DRB1/genética , Ásia , Etnicidade , Europa (Continente) , Frequência do Gene , Variação Genética , Genética Populacional , Genótipo , Haplótipos , Humanos , Oceania , Grupos Populacionais
15.
Int J Immunogenet ; 39(1): 79-81, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22010883

RESUMO

Using PCR with sequence-specific primers (SSP) and subsequent sequencing of exons 2 and 3, we identified an example of B*15:33 in a likely north-western European Caucasoid volunteer haemopoietic stem cell (HSC) donor. This was only the second example submitted to the IMGT/HLA database since B*15:33 was first described in 1996. B*15:33 differs from B*15:01:01:01 by three nucleotides resulting in two amino acid differences with B*15:01 (131S>R, 138T>K). This allele encodes a typical HLA-B62 specificity--as confirmed using 17 local antisera from parous women and 19 monoclonal antibodies directed towards B15, B62 and B63 specificities. Importantly, it also reacted as a Cw5/Cw8 specificity when tested against 21 Cw5, Cw5/Cw8 and Cw8 antisera. This Cw5/Cw8 reactivity is probably due to the B*15:33 specificity having lysine at position 138 which is possessed by numerous C*05 and many C*08 products. B*15:33 is likely to have derived from a HLA-B/C inter-locus gene conversion event. HLA-B*15:33 is clearly rare--this single example was found during the HLA PCR-SSP-based typing of 57,079 potential HSC donors. This indicates an allele frequency of <0.00001 in blood donors resident in Wales. An Epstein-Barr virus transformed B-cell line from the HLA-B*15:33 donor is available.


Assuntos
Alelos , Reações Antígeno-Anticorpo , Epitopos , Antígeno HLA-B15/genética , Antígenos HLA-C/imunologia , Motivos de Aminoácidos , Sequência de Bases , Linhagem Celular Transformada , Primers do DNA/genética , Éxons , Feminino , Frequência do Gene , Antígeno HLA-B15/imunologia , Antígenos HLA-C/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência , Doadores de Tecidos
16.
Int J Immunogenet ; 39(5): 394-408, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22520580

RESUMO

We have characterized the HLA-A, -B, -DRB1, -DQA1 and -DQB1 profiles of three major ethnic groups living in Chelyabinsk Region of Russian South Urals, viz., Russians (n = 207), Bashkirs (n = 146) and Tatars (n = 135). First field level typing was performed by PCR using sequence-specific primers. Estimates included carriage and gene frequencies, linkage disequilibrium and its significance and related values. Population comparisons were made between the allele family frequencies of the three populations and between these populations and 20 others using a dendrogram. Chelyabinsk Region Russians demonstrate all the features typical of a Caucasoid population, but also have some peculiarities. Together with Tatars, Russians have high frequencies of allele families and haplotypes characteristic of Finno-Ugric populations. This presupposes a Finno-Ugric impact on Russian and Tatar ethnogenesis. However, this was not apparent in Bashkirs, the first of the three populations to live in this territory, and implies admixture with populations of a Finno-Ugric origin with precursors of Russians and Tatars before they came to the South Urals. The Bashkirs appear close to Mongoloids in allele and haplotype distribution. However, Bashkirs cannot be labelled either as typical Mongoloids or as Caucasoids. Thus, Bashkirs possess some alleles and haplotypes frequent in Mongoloids, which supports the Turkic impact on Bashkir ethnogenesis, but also possess the AH 8.1 haplotype, which could evidence an ancient Caucasoid population that took part in their ethnic formation or of recent admixture with adjacent populations (Russians and Tatars). Bashkirs showed no features of populations with a substantial Finno-Ugric component, for example Chuvashes or Russian Saami. This disputes the commonly held belief of a Finno-Ugric origin for Bashkirs. Tatars appeared close to many European populations. However, they possessed some characteristics of Asiatic populations possibly reflecting a Mongoloid influence on Tatar ethnogenesis. Some aspects of HLA in Tatars appeared close to Chuvashes and Bulgarians, thus supporting the view that Tatars may be descendents of ancient Bulgars.


Assuntos
Povo Asiático/genética , Etnicidade/genética , Frequência do Gene , Antígenos HLA-A/genética , Haplótipos , Adolescente , Adulto , Alelos , Feminino , Genética Populacional/métodos , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Teste de Histocompatibilidade/métodos , Homozigoto , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Federação Russa/etnologia , Adulto Jovem
17.
Tissue Antigens ; 78(4): 296, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21644932

RESUMO

HLA-DQB1*02:01:04 differs from DQB1*02:01:01 by one nucleotide (G>A) at position 303 in exon 2 resulting in a silent substitution (codon 69 - GAG >GAA), conserved glutamate.


Assuntos
Éxons/genética , Cadeias beta de HLA-DQ/genética , Mutação Puntual , Feminino , Humanos , Masculino , Garantia da Qualidade dos Cuidados de Saúde
18.
Tissue Antigens ; 78(6): 459-60, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21749330

RESUMO

HLA-C*08:43 differs from HLA-C*08:02:01 by one nucleotide (A>G) at position 584 resulting in an amino acid change of 171 tyrosine to 171 cysteine.


Assuntos
Alelos , Substituição de Aminoácidos , Antígenos HLA-C/genética , Mutação de Sentido Incorreto , Humanos
19.
Int J Immunogenet ; 38(2): 161-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21208379

RESUMO

A new allele, HLA-B*40:92, was identified in a north-western European subject during polymerase chain reaction using sequence-specific priming (PCR-SSP)-based typing of haematopoietic stem cell (HSC) donors. B*40:92 differs from B*40:01:01 by six nucleotides at positions 559, 560, 603, 605, 610 and 618 in exon 3 which represents a substitution motif of at least 60 nucleotides. This motif, which occurs in numerous HLA alleles including the relatively high frequency B*15 and B*35 allele families, encode four amino acid changes at positions 163 (glutamic acid > leucine), 177 (aspartic acid > glutamic acid), 178 (lysine > threonine), 180 (glutamic acid > glutamine) and a silent substitution, conserved alanine, at codon 182. Thus, it is likely that HLA-B*40:92 occurred following a gene conversion-like or interallelic recombination event involving B*40:01:01 and probably a B*15 or more likely a B*35 family allele. HLA-B*40:92 was found on a haplotype with HLA-A*02:01, B*40:92, C*03:04, DRB1*13:02, DRB3*03:01, DQA1*01:02, DQB1*06:04, DPA1*02:02, DPB1*05:01. Tests on 69 selected B40 and B35 antisera and Lambda Monoclonal Trays™ show that B*40:92 encodes a 'short' B40/B60 serological specificity which displays some HLA-B35 reactivity. The HLA-B40 and HLA-B35 motifs (possible epitopes) responsible for this serological reactivity were identified. This single example of HLA- B*40:92 was found in 56,823 consecutive HLA PCR-SSP typed HSC donors indicating a carriage frequency of 0.00176% (allele frequency 0.00001) in blood donors resident in Wales. An Epstein-Barr virus transformed B-cell line from the HLA-B*40:92 donor is available.


Assuntos
Alelos , Antígenos HLA-B/genética , Especificidade de Anticorpos/imunologia , Sequência de Bases , Éxons/genética , Antígenos HLA-B/imunologia , Antígeno HLA-B40 , Humanos , Dados de Sequência Molecular , Sequências Reguladoras de Ácido Nucleico/genética , Alinhamento de Sequência
20.
Tissue Antigens ; 76(3): 255-6, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20492593

RESUMO

HLA-DRB1*0343 differs from DRB1*0330 by one nucleotide (G > C) resulting in an amino acid change of 38valine to 38leucine.


Assuntos
Doadores de Sangue , Antígenos HLA-DR/genética , Alelos , Substituição de Aminoácidos , Linfócitos B , Feminino , Cadeias HLA-DRB1 , Células-Tronco Hematopoéticas , Humanos , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
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