A novel HLA-B*51 allele, HLA-B*5149

Discovery of the novel HLA-B*5149 allele in a North American Caucasian individual is described. It differs from B*510101 by one nucleotide within the coding sequence of exons 1-6. A substitution at nucleotide position 488 in exon 3 changes alanine to glycine in amino acid position 139.     

Identification of three novel HLA class I alleles: HLA-B*3928, HLA-B*400104 and HLA-B*4437

Three new human leukocyte antigen (HLA) class I alleles have been identified in the Tissue Typing Laboratory in Sydney, Australia. Sequence analysis of exon 2 and exon 3 of the HLA-B gene revealed the novel polymorphism. A silent substitution of C to T at nucleotide position 369 has been identified for the HLA-B*400104 allele when compared to the closest matched allele, HLA-B*400101. The HLA-B*3928 allele was identified with a nucleotide substitution of G to C at position 362 when compared to the closest matched allele, HLA-B*390101, resulting in an amino acid substitution of Arginine to Threonine. A nucleotide substitution of C to G at position 572 resulting in the amino acid change Serine to Tryptophan was identified in the new allele HLA-B*4437, when compared to the closest matched allele HLA-B*440301. Both amino acid substitutions implicate a different specificity and affinity of antigen binding for the alleles HLA-B*3928 and HLA-B*4437.     

Identification of a new HLA-B*39 allele: HLA-B*3924

We have identified a new HLA-B*39 allele through polymerase chain reaction (PCR) using sequence-specific primers (SSP) and sequence-based typing of exons 2 and 3. This novel allele was identified in three HLA-identical siblings of Turkish origin. This allele only differs from HLA-B*3903 at a unique single nucleotide substitution (T for C) at position 365 in exon 3 which results in an amino acid change in codon 98 of methionine (ATG) to threonine (ACG). The sequencing enabled the development of a monospecific PCR-SSP reaction which can be used to discriminate between HLA-B*3924 and other B*39 alleles.     

Identification of a new HLA-B*08 variant, HLA-B*0804

The HLA-B locus is the most polymorphic locus known with currently over 100 different alleles described. Many of these alleles encode variants of the serologically-defined tissue transplantation antigens. This high level of diversity makes accurate tissue typing difficult. Here we present the sequence of a new HLA-B *08 variant, HLA-B *0804. found in Caucasian siblings JH and PF serologically typed as HLA-B51/B59 and HLA-B59/B60, respectively. Additionally, DNA-based typing by the polymerase chain reaction using sequence-specific primers (PCR-SSP) identified HLA-B *51 in JH and HLA-B *4001 in PF. However, PCR-SSP failed to identify a second allele in either of these individuals. The unusual finding of a B59 antigen in a Caucasian and the discrepant molecular typing results suggested that these individuals might express novel HLA molecules. Using denaturing gradient gel electrophoresis (DGGE) followed by direct sequencing, we characterized a novel HLA-B *08 variant, HLA-B *0804. The presence of this allele was confirmed by cloning and sequencing. HLA-B *0804 differed from HLA-B *0801 by only one nucleotide substitution resulting in an amino acid replacement of phenylalanine by serine at position 67. Incidentally, this single nucleotide difference was sufficient to prevent amplification by PCR-SSP. This striking difference between both the serologically typed antigen and the PCR-SSP-identified allele compared to the sequenced allele supports the use of sequence-based typing for the analysis of HLA class I locus alleles.     

HLA-B*0749N: the first HLA-B*07 null allele

In the present article, we report the identification of the first HLA-B*07 null allele found in a Polish patient awaiting a kidney allograft. A discrepant result obtained between serological typing (HLA-B "blank") and high-resolution molecular typing using PCR-SSP method (HLA-B*070201 allele) suggested the presence of a null allele. Genomic DNA sequencing of the HLA-B*07 allele revealed a single nucleotide substitution at the 3' end of the exon 4 leading to a premature stop codon.     

Identification of a new HLA-B*15 allele,HLA-B*1569

We have identified a new HLA-B*15 allele (B*1569) by polymerase chain reaction (PCR) using sequence-specific primers (SSP) and sequence-based typing (SBT). This novel allele was found in a 67-year-old white Caucasian male and differs from HLA-B*1503 at 3 positions. The nucleotide substitutions at positions 544, 559 and 560 result in amino acid changes at codon 158 from GCC (alanine) to ACC (threonine), and at codon 163 from CTG (leucine) to ACG (threonine).     

Characterization of two new HLA-B alleles by sequence-based typing: HLA-B*0817 and HLA-B*1311

In this brief communication we report the characterization of two new HLA-B variants officially named HLA-B*0817 and HLA-B*1311. The HLA-B*0817 allele was identified in a Caucasoid male candidate for renal transplantation in the North Italy Transplant program. The nucleotidic sequence of exons 2, 3 and 4 of this novel allele is identical to that of HLA-B*0804 except for three point mutations in exon 2: from A to G at position 259, from C to G at position 261 and from G to A at position 302. These mutations are responsible for two aminoacidic substitutions [Asn (r) Glu, codon 63, and Ser (r) Asn, codon 77]. HLA-B*1311 was found in a volunteer donor belonging to National Marrow Donor Program(R). This new variant is identical to that of HLA-B*1301 except for three nucleotide substitutions at positions 353, 355 and 369 leading to two aminoacidic variations from Ile to Thr at codon 94 and from Ile to Leu at codon 95 and a silent mutation at codon 99.     

Characterization of three novel HLA alleles, HLA-B*4613, HLA-B*4614 and HLA-B*4618, in Chinese individuals

Three novel alleles, human leukocyte antigen (HLA)-B*4613, HLA-B*4614 and HLA-B*4618, were identified in Chinese individuals. HLA-B*4613 shows four nucleotides difference from B*460101, resulting in two amino acids change from Glu to Val at codon 152 and Trp to Leu at codon 156. HLA-B*4614 has a single nucleotide difference at position 97 T→C compared with HLA-B*460101, with an amino acid change from Tyr to His at codon 9. HLA-B*4618 shares the sequence of exon 2 with B*4601 and sequences of exons 3 and 4 with B*55, B*54 or B*59, together resulting in eight amino acids change compared with HLA-B*460101.     

Identification of two new HLA-B alleles, HLA-B*0732 and HLA-B*5809, by sequence-based typing

Here, we have described the characterization of two novel human leukocyte antigen-B (HLA-B) alleles. The new alleles, HLA-B*0732 and HLA-B*5809, were identified in Italian Caucasian individuals. B*0732 differs from HLA-B*0708 by one nucleotidic change at position 412 (from G to A) in exon 3, leading to an amino acidic substitution from Asp (GAC) to Asn (AAC) at codon 114. The sequence of B*5809 is identical to that of HLA-B*5801, except for a point mutation at position 583 in exon 3, where a T is substituted by a C. This change leads to an amino acidic substitution from Tyr (TAC) to His (CAC) at codon 171.     

HLA-B*4431: a new HLA-B variant with a complex ancestral history involving HLA-B*44, B*40 and B*07 alleles

We here describe the identification of the new allele HLA-B*4431, which was found in three members of a Turkish family. Sequencing of the new allele following haplotype-specific PCR amplification revealed that exon 2 is identical to HLA-B*4402, whereas exon 3 resembles a HLA-B*40 variant with the exception of position 572, where a single nucleotide transversion (C > G) leads to an amino acid exchange (Trp162Ser). The generation of the 3' part of B*4431 may be best explained by a separate recombination between B*40 and B*07. Although B*4431 consists of B44 in its alpha1 domain and of B60(40) in its alpha2 domain; the new allele only displayed B44 seroreactivity, which demonstrates that epitopes crucial for B60(40) specificity must be located in the alpha1 domain.     

Identification of HLA-B*1566

A novel polymorphism was identified in a B*15 allele. B*1566 possesses a nucleotide substitution of C to G at nucleotide 272. This polymorphism encodes an amino acid difference from serine in B*1501101 to cysteine in B*1566 at residue 67. Residue 67 is a constituent of the B pocket and is situated on the alpha1 helix facing into the groove. This mutation may have arisen through interallelic recombination as it has been seen in other B*15 alleles and is also present in most B*14, B*27, B*38, B*39 alleles and in B*7301.     

Identification of HLA-B*0722

A novel polymorphism was identified in a B*07 allele. B*0722 possesses a unique nucleotide substitution at nucleotide 481. This polymorphism encodes an amino acid difference from aspartic acid in B*07021 to asparagine in B*0722. The functional significance of this polymorphism on peptide binding and/or T-cell recognition is unknown.     

Description of a new HLA-B allele: HLA-B*4077

HLA-B*4077 differs from B*400101, B*4036, and B*401401 in five, four, and three nucleotides, respectively. However, amino acid alignment would indicate a closer relationship with B*4036 allele, showing a single amino acid replacement at codon 131 (R>S).     

Characterization of a new HLA-B allele, HLA-B*5312, and re-evaluation of the published sequences of the untranslated regions of HLA-B*35 and HLA-B*53

We report a novel human leukocyte antigen (HLA)-B allele, HLA-B*5312. Compared with HLA-B*530101, there is one silent substitution at nucleotide 438 and two non-synonymous substitutions at nucleotides 431 and 440, causing a change of the amino acid sequence (Asn-->Ser at codon 77 and Ile-->Thr at codon 80, respectively) within the Bw4 epitope. In contrast to the published sequences (IMGT/HLA Database, version 2.16.0, January 2007), we found that HLA-B*530101 had a C instead of a T at nucleotide -221, whereas HLA-B*350101 had a C instead of an A at nucleotide 2992. According to our sequencing results, HLA-B*5312 resembles HLA-B*350101 regarding its sequence of the untranslated regions. HLA-B*5312 may have been the result of a double crossing over event during which HLA-B*350101 adopted a Bw4 motif.     

Identification of two new HLA-B22 variants, HLA-B*5509 and B*5606

In our recent study using high-resolution HLA-B locus typing by sequence-based typing (SBT) we identified 9 new alleles in a total of 355 unrelated individuals (4). Three of them concerned an allele belonging to the B22 group. One of them, B*5607, showed the unusual presence of a Bw4 sequence motif, as described previously (5). In this report the other two B22 variants are described; one belonging to the B55 specificity and named B*5509; the other one being a B*56 allele and assigned B*5606, which brings the total number of alleles belonging to the B22 group to 18.