Two DR2-associated novel alleles arose from the silent mutation of codon 72: DRB1*16012, DRB5*01012.
Two DRB1*02-associated alleles, DRB1*16012 and DRB5*01012, are described. Both alleles carry the same silent substitution at codon 72.
Alleles↗
Biomedical subjects
C K Hurley
Publications and source records attributed to C K Hurley.
The HLA dictionary 1999: a summary of HLA-A, -B, -C, -DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens.
This report presents serologic equivalents of 90 HLA-A, 190 HLA-B and 145 HLA-DRB1 alleles. The equivalents cover over 70% of the presently identified HLA-A, -B and -DRB1 alleles. The dictionary is an update of the one published in 1997 and now also includes equivalents for HLA-C, DRB3, DRB4, DRB5 and DQB1 alleles. The data summarize information obtained by the WHO HLA Nomenclature Committee, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP) and by individual laboratories. In addition, a listing is provided of alleles which are expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities and that often lack official WHO nomenclature. The provided equivalents will be useful in guiding searches for unrelated donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programs where HLA typings from donors and from recipients on waiting lists represent mixtures of serologic and molecular typings. Some guidelines are provided for the use of appropriate WHO HLA nomenclature for serological typings and for generic and allele specific typings obtained with molecular methods. The tables with HLA equivalents and the questionnaire for submission of serology on poorly identified alleles will also be available at the WMDA web page: www:bmdw.org/wmda.
Alleles↗
Histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors: report from The World Marrow Donor Association. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association.
The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. The ability to identify unrelated stem cell donors in one country for patients in another country requires cooperation and standardization in many areas. The adoption of guidelines for histocompatibility testing, such as those summarized in this report, will facilitate these opportunities and rapidly provide accurately typed donors for patients in need.
Adult↗
Sequence of an HLA-B56 variant (B*5604) identified in the Korean population.
Three alleles encoding molecules with the B56 serologic specificity have been reported thus far. This study characterized an additional allele encoding a B56 molecule from two unrelated Korean individuals. The novel allele, B*5604, differs from B*5602 by a single nucleotide substitution at codon 103 (CTG-->GTG) resulting in an amino acid change from leucine to valine. The putative haplotype associated with the novel allele was A2-B*5604-Bw6-Cw7-DRB1*15-DRB5*02-DQA1*01-DQB 1*05.
Alleles↗
Clarification of HLA-B serologically ambiguous types by automated DNA sequencing.
Assignment of HLA-B types can be hampered by ambiguous reactivity of the typing sera resulting in inaccurate HLA-B assignments. In this study, 19 Korean samples exhibiting ambiguous serologic reactivities were characterized by DNA sequencing. Alleles identified from 7 samples were previously undetected in this population (B*1517, B*4101, B*4701, B*5001, and B*5106) and from 9 samples were common alleles in this population (B*4002, B*4003, B*4006, B*1501, B*1401, B*67012, and B*5401). Three samples were putative HLA-B homozygotes. Three major factors causing serologic ambiguity were identified: weak or false negative reactivity of typing sera (52.4%); cross or false positive reactivity of the sera (38.1%); and absence of information on the reaction patterns due to the lack of appropriate sera in the typing kit (e.g. B*4101 encoded molecule) or to the presence of recently characterized molecules (e.g. B*5106 encoded molecule) (9.5%). Overall, sequencing was helpful in clarifying ambiguous serologic reaction patterns improving the HLA typing for the Korean population.
Alleles↗
Novel HLA-A and HLA-B alleles.
Nine novel HLA-A and HLA-B alleles are described: A*2609, A*6803, A*6806, B*1539, B*1540, B*2712, B*4103, B*5109, and B*5603. Most appear to have arisen by gene conversion events. B*5603 appears to have arisen by a reciprocal recombination event joining exon 2 of a B*55/ *56 allele with exon 3 of a B*15 allele. Serologically, the antigen encoded by this allele types with broad B22- and Bw6-specific alloantisera. Also unique, the antigen encoded by B*2712 does not react with B27-specific alloantisera but does react with Bw6-specific alloantisera.
Alleles↗
Diversity associated with the second expressed HLA-DRB locus in the human population.
Although diversity within the HLA-DRB region is predominantly focused in the DRB1 gene, the second expressed DRB loci, DRB3, DRB4, and DRB5, also exhibit variation. Within DRB1(*)15 or DRB1(*)16 haplotypes, four new variants were identified: 1) two new DRB5 alleles, DRB5*0104 and DRB5*0204, 2) a haplotype carrying a DRB1(*)15 or *16 allele without the usual accompanying DRB5 allele, and 3) a haplotype carrying a DRB5(*)0101 allele without a DRB1(*)15 or *16 allele. The evolutionary origins of these haplotypes were postulated based on their associations with the DRB6 pseudogene. Within HLA haplotypes which carry DRB3, a new DRB3(*)0205 allele and one unusual DRB3 association were identified. Finally, two new null DRB4 alleles are described: DRB4(*)0201N, which exhibits a deletion in the second exon, and a second allele, DRB4(*)null, which lacks the second exon completely. Gene conversion-like events and variation in the number of functional genes through reciprocal recombination and inactivation contribute to the diversity observed in the second expressed HLA-DRB loci.
Alleles↗
Donor work-up and transport of bone marrow--recommendations and requirements for a standardized practice throughout the world from the Donor Registries and Quality Assurance Working Groups of the World Marrow Donor Association (WMDA).
In October 1995 the World Marrow Donor Association (WMDA) was restructured in order to facilitate its primary function of establishing guidelines in relation to international bone marrow and blood stem cell transplants -- transplants in which the donor is in one country and the patient is in another country. Five new working groups were established -- Donor Registries, Ethics, Quality Assurance, Finances, and Stem Cells. This paper, prepared by members of the Donor Registries Working Group, in consultation with the Quality Assurance Working Group, provides recommendations for the 'donor work-up'. This term covers events that start when the definitive donor has been identified, includes the harvesting (collection) and transportation of the stem cell product and ends when the product reaches the transplant centre. The paper includes examples of the documentation intended to ensure compliance with the recommendations at all key points in the sequence.
Bone Marrow Transplantation↗
Diversity and evolution of the DRB1*03 family: description of DRB1*03022,*0307,*0308.
Three previously unreported DRB1*03 alleles are described, adding to the diversity of the DRB1 family of alleles. DRB1*03022 contains a silent substitution at codon 77. DRB1*0307 differs from DRB1*03011 by a substitution at codon 26 resulting in a predicted change from tyrosine to phenylalanine. DRB1*0308 is almost identical to DRB1*03011 differing at codon 58 which specifies the glutamic acid residue commonly found in DRB1*11 alleles. The new alleles (DRB1*03022,*0307,*0308) may have arisen by gene conversion-like events and add to the increasing complexity of the HLA system.
Alleles↗
Acquisition and use of DNA-based HLA typing data in bone marrow registries.
The increased use of DNA-based typing techniques has improved the accuracy and reliability of HLA types assigned to patients requiring an allogeneic bone marrow transplant and their potential donors, facilitating better donor selection. The benefits of this technology, which will completely replace serologic typing within the next few years, have not yet been fully exploited since the typing information obtained in the form of DNA sequence polymorphisms is presently converted to an HLA allelic type for submission to a registry. Furthermore, within the registry, the allelic type may be further converted to a serologic antigen for use in the search and match process. Because the current nomenclature system makes selection of donors who are likely to provide optimal matches difficult, it is critical that DNA-based HLA typing data be recorded by registries as sequence polymorphisms tested as positive or negative rather than interpreted HLA types and that searching and matching utilize these polymorphisms. Until this transition is complete, we will not fully utilize this powerful HLA typing technology to best serve those patients seeking unrelated donors.
Alleles↗
Identification of four new DR52-associated DRB1 alleles: DRB1*1424, *1425, *1323 and *1324.
Four previously unreported DR52-associated DRB1 alleles have been characterized through DNA sequencing, contributing to the diversity of the HLA system. DRB1*1424 is nearly identical to DRB1*1402 in the second exon, except that it contains the "I---A" motif found at codons 67-71 common to the DRB1*15 alleles. DRB1*1425 contains the "A--H" motif, found in DRB1*1401 at codons 57-60, in a sequence otherwise identical with the second exon of DRB1*1307. Compared with DRB1*11012, DRB1*1323 contains three predicted amino acid changes at codons 58 (ala-->glu), 67 (phe-->ile), and 71 (arg-->glu). The sequence of DRB1*1324 is identical to exon 2 of DRB1*1103, except that DRB1*1324 does not contain the GAG at codon 58 characteristic of the DRB1*11 alleles. These new alleles may have arisen through gene conversion, and they contribute to the complexity of the DR6 family.
Alleles↗
Characterization of a novel HLA-B allele, B*0804, in a Norwegian family.
Explore the source record for details and available documents.
Alleles↗
Analysis of HLA-A and -B serologic typing of bone marrow registry donors using polymerase chain reaction with sequence-specific oligonucleotide probes and DNA sequencing.
Unrelated volunteer donors (69) recruited by the National Marrow Donor Program were HLA typed by DNA-based methods for both the HLA-A and -B loci. Each donor had been previously typed by serology by at least two independent laboratories. Of the 69 samples, all serologic laboratories were in concordance for HLA-A in 62 typed samples and for HLA-B in 48 typed samples. Of the serologically concordant samples, 5 samples typed for HLA-A and 7 samples typed for HLA-B received DNA and serology types differing in their level of resolution. One sample typed for HLA-A and 3 samples typed for HLA-B by DNA methods gave different results from their serologic assignments. Of the samples exhibiting disparities among the different serologic typing laboratories, the DNA-defined types of 7 samples typed for HLA-A and 18 samples typed for HLA-B were consistent with at least one of the serologic assignments. The DNA types for the remaining 3 HLA-B typed samples did not agree with the serologic assignments and their alleles were subsequently sequenced. One of these sequences was a previously undefined allele, B*1537. Sharing of polymorphic sequences among HLA allelic products creates difficulties for consistent serologic assignments of some types complicating the process of identifying potential donors from bone marrow registries. Thus, the use of DNA-based typing techniques for characterization of donor class I types should allow a more consistent definition of types and should speed the donor selection process.
Bone Marrow Transplantation↗
The search for HLA-matched donors: a summary of HLA-A*, -B*, -DRB1/3/4/5* alleles and their association with serologically defined HLA-A, -B, -DR antigens.
This report summarizes data obtained from several large studies including the WHO HLA Nomenclature Committee, the International Cell Exchange, UCLA, the British Society for Histocompatibility and Immunogenetics Rare Cell Exchange and the National Marrow Donor Program and individual laboratories aimed at identifying a serologic type for specific HLA-A,-B,-DRB allelic products. Alleles that are poorly characterized at the serologic level are indicated and an approach is suggested for obtaining the information needed to clarify their serologic typing. The tables provided will be useful in guiding searches for an unrelated donor in which patient and/or potential donors are typed either by serology or by DNA-based methods and will provide a "dictionary" of potential equivalents between HLA "types" obtained by the two methods.
Alleles↗
Characterization of an HLA-B62 variant (B*1538) exhibiting an additional B52 serologic reactivity.
Antigens bearing the B62 serologic specificity are a heterogeneous group being encoded by at least 10 alleles and are widespread in most populations including the Korean population (10.5%). This study characterized a new allele encoding a B62 molecule with extra B52 serologic reactivity from a Korean family and unrelated individuals. Based on the DNA sequence, it appears that the single nucleotide substitution at codon 171 (TAC-->CAC), resulting in an amino acid change from tyrosine to histidine, is responsible for creating the extra reactivity. B*1538 was confirmed by PCR-SSP using a primer annealing to codon 171 in two additional unrelated individuals also exhibiting the same serologic reaction pattern. The haplotype associated with the novel allele, A31-B*1538-Bw6-Cw3-DRB1*1101-DRB3*02-DQB1*0301, was identified in the family members and two unrelated individuals. The novel B*1538 allele and its associated haplotype adds to the HLA diversity in this population.
Genetic Variation↗
Molecular interactions between transfected human TCR, immunodominant myelin basic protein peptide 152-165, and HLA-DR13.
Chimeric TCR transfectants expressing human extracellular sequences and murine intracellular/transmembrane sequences were generated to analyze the trimolecular interaction between myelin basic protein (MBP) autoantigen, HLA, and a TCR isolated from a patient with multiple sclerosis. Chimeric transfectants responded to TCR activation by CD3- and TCRBV22S1-specific mAbs and by superantigen. Additionally, chimeric transfectants responded to autoantigen-specific activation with MBP 152-165 when presented by DR(alpha,beta1*1301) independent of the CD4 adhesion molecule. Transfectants did not respond to Ag presented by other HLA-DR molecules, including the closely related DR(alpha,beta1*1302). In peptide-binding studies with a panel of serial alanine-substituted MBP peptides, HLA contact residues necessary for anchoring MBP 152-165 to DR(alpha,beta1*1301) were also defined: 154 (F), 159 (R), and 162 (R). The chimeric TCR transfectant's differential response to a similar panel of MBP analogues defined residues that interact with the TCR: 153 (I), 155 (K), 156 (L), 160 (D), and 161 (S). Analysis of molecular interactions, such as those described in this work, may be central to developing new strategies for suppressing Ag-specific responses in human autoimmune disease.
Amino Acid Sequence↗
Diverse usage of human T-cell receptor gene segments in HLA-DR1 allospecific T-cell clones.
T-cell recognition of alloantigen involves both the MHC molecule and its associated peptide ligand. To understand the relationship between the specificity of alloantigen recognition and the structure of TCR molecules, we have investigated TCR gene utilization by sequencing TCR genes from well-defined allospecific T-lymphocyte clones. Alloreactive TLC consisted of a panel of clones primed to recognize DR1-related alloantigens. Our sequencing results revealed extensively diverse, but nonrandom, usage of TCR AV and BV gene segments and essentially no conservation in CDR3 or junctional sequences. Such observations are consistent with allospecific TCR that interact with MHC molecules on a generic level while recognizing specific peptides. They also reduce potential enthusiasm for anti-TCR therapy in allograft rejection.
Amino Acid Sequence↗
The impact of DR3 microvariation on peptide binding: the combinations of specific DR beta residues critical to binding differ for different peptides.
HLA-DR molecules are a group of highly polymorphic glycoprotein heterodimers that present peptide antigens to T lymphocytes for immune surveillance. To assess the significance of limited polymorphism on the functional differentiation of DR molecules, the binding of several immunogenic peptides to the DR3 microvariants [DR(alpha, beta 1*0302) and DR(alpha, beta 1*0301)] and to mutants of these DR3 molecules was examined. This analysis has shown that each residue (DR beta 26, DR beta 28, DR beta 47, and DR beta 86), which differentiates these two DR3 molecules, contributes to their functional distinction and that the relative contribution of each residue varies for different peptide/DR3 complexes. For example, DR beta 28 and DR beta 86 controlled the mycobacterium tuberculosis 65-kD heat shock protein peptides 3-13 and 4-15 (HSP) binding specificity to DR (alpha, beta 1*0301). [HSP does not bind to DR(alpha, beta 1*0302)], whereas DR beta 26, DR beta 28, and DR beta 86 controlled the influenza hemagglutinin peptide 306-318 (HA) binding specificity to DR(alpha, beta 1*0302). [HA does not bind to DR(alpha, beta 1*0301).] In comparison, DR beta 86 alone controlled the binding level difference of sperm whale myoglobin peptide 132-151 (SWM) and of myelin basic protein peptide 152-170 (MBP) [both bind to DR(alpha, beta 1*0301) at levels five times greater than to DR(alpha, beta 1*0302)] to the DR3 molecules. Although not critical, additional DR beta residues influenced the binding level of individual peptides of each of the DR3 molecules and, again, the combinations of these residues differed for different peptide/DR3 complexes. These data showed that individual DR residues vary in their relative contribution to the interaction between a specific DR molecule and different peptides and that limited polymorphism can create substantial differences in the peptide binding profiles among DR molecules.
Amino Acid Sequence↗