An update to HLA nomenclature, 2010.

The WHO Nomenclature Committee for Factors of the HLA System met during the 15th International Histocompatibility and Immunogenetics Workshop in Buzios, Brazil in September 2008. This update is an extract of the main report that documents the additions and revisions to the nomenclature of human leukocyte antigen (HLA) specificities following the principles established in previous reports.

Association of MICA-TM and MICB C1_2_A microsatellite polymorphisms with tumor progression in patients with colorectal cancer.

PURPOSE: The major histocompatibility complex class I related A (MICA) and MICB molecules are ligands of NKG2D receptors on natural killer cells, gamma/delta T cells, and CD8ass T cells that mediate host antitumor immune response. The role of MICA-TM and MICB C1_2_A alleles in patients with colorectal cancer has not yet been investigated. METHODS: We have analyzed the MICA-TM and MICB C1_2_A polymorphisms in colorectal cancer patients (n = 79) by polymerase chain reaction amplification, subsequent electrophoresis, and sequencing in comparison to a previously analyzed cohort of healthy controls (n = 306). Allele frequencies obtained for MICA-TM and MICB C1_2_A were compared to histopathological data regarding tumor invasion, disease progression, microsatellite instability, and the presence of KRAS mutations (codon 12) and analyzed for possible impact on tumor-related survival (n = 61). RESULTS: Allele frequencies of MICA-TM and MICB C1_2_A polymorphisms were not different in patients with colorectal cancer in comparison to normal controls. In colorectal cancer patients, MICA-TM A4 allele was directly and MICA-TM A5 allele was inversely associated with lymph node involvement and advanced UICC stages. Tumor-related survival in colorectal cancer patients was significantly reduced in the presence of the MICA-TM A4 allele (p = 0.015). In patients with microsatellite stable tumors, survival was reduced in association with the MICA-TM A4 allele (p = 0.006) and MICA-TM A9 allele (p = 0.034), but increased in patients showing the MICA-TM A5 allele (p = 0.042). CONCLUSIONS: Specific MICA-TM alleles seem to influence tumor progression and midterm survival of patients with colorectal cancer, indicating an important role of host innate immune predisposition involving NKG2D mediated antitumor response.

Bone marrow donor routine HLA typing identified a novel B*55 allele, B*5517, confirmed by allele-specific DNA cycle sequencing.

In this article, we report the identification of a new human leukocyte antigen-B allele in a sample that was tested in our routine typing for volunteer bone marrow donors. This novel allele officially designed B*5517 was found in a male donor of Bavarian Caucasoid origin (Laboratory code 150113). The search for unrelated bone marrow donors was initiated by the Aktion Knochenmarkspende Bayern. In comparison with the common B*5501 allele, B*5517 differs at three nucleotide positions all located in exon 3, at position 379 (C-->G), 419 (T-->A), and 420 (A-->C), resulting in two amino acid substitutions at codons 127 and 140. The amino acid 127, leucine, is changed to valine, and the amino acid 140, also a leucine, is replaced by tyrosine in B*5517.

A novel A*24 allele, A*2442, was detected through routine bone marrow donor screening.

In this article, we report the identification of a new HLA-A allele found in a DNA sample which was part of the routine bone marrow donor typing performed in our laboratory. This novel allele officially designated as A*2442 was found in a sample from a female Caucasoid donor (Franken, Bavaria, Germany; lab code 142654) and differs from the closest related allele A*2408 by two nucleotide exchanges. In position 81, the A (A*2408) is changed to 81 C in the novel allele A*2442, resulting in an amino acid substitution at codon 27, glutamine (A*2408) is replaced by histidine ((31)Gln-->(31)His). In position 292, the G (A*2408) is changed to C also resulting in an amino acid replacement, the codon 98 asparagine is mutated to histidine ((98)Asn-->(98)His) in the new A*2442 allele. The second allele was determined to be A*0301. Further typing of this sample is B*1501 B*4001.

Bone marrow donor routine HLA typing identified a novel B*07 allele, B*0734, confirmed by allele-specific DNA cycle sequencing.

In this article, we report the identification of a new human leukocyte antigen-B allele in a sample that was tested in our routine typing for bone marrow donors. This novel allele officially designed B*0734 was found in a female donor of Bavarian Caucasoid origin (Laboratory code 121036). The search for unrelated bone marrow donors was initiated by the Aktion Knochenmarkspende Bayern. In comparison to the common B*070201, B*0734 differs at four nucleotide positions, 412 (G-->A), 539 (G-->T), 559 (G-->A) and 560 (A-->C) causing three amino acid substitutions, at postion 138 Asp-->Asn, at position 180 Arg-->Leu and at position 187 Glu-->Thr.

A novel HLA-B*55 allele, HLA-B*5514, found in a DNA sample derived from a bone marrow donor.

In this study, we report the identification of a new human leucocyte antigen-B (HLA-B) allele in a sample that was found in our routine typing. This novel allele, officially designed HLA-B*5514, was found in a male donor of Bavarian Caucasoid origin (Laboratory code: 117562) typed in order for a request of the bone marrow donor registry Aktion Knochenmarkspende Bayern. Although this novel allele was added to the HLA-B*55 family by the Nomenclature Committee, the next related alleles were found in the HLA-B*56 group; HLA-B*5612 differing in six positions from HLA-B*5514 is the closest related allele.

Sequence-based typing confirmed a novel B*40 allele, B*4046, which was identified through sequence-specific oligonucleotide hybridization routine typing.

In this paper, we report the identification of a new human leucocyte antigen-B (HLA-B) allele in a sample which has participated in a search for unrelated bone marrow donors which was initiated by the Aktion Knochenmarkspende Bayern. This novel allele officially designed B*4046 was detected by different low-resolution sequence-specific oligonucleotide typings not matching to known allele combinations in a female Caucasoid individual. Confirming the presence of a novel allele by sequence-based typing, the closest-related allele B*400103 differs from the new B*4046 allele by three mutations. This results in an amino acid substitution from threonine to alanine in B*4046 at codon 65, while codon 68 remains conserved and codon 69 "AAG" lysine is replaced by "GAG" glutamic acid in B*4046.

A novel B*38 allele, B*3809, was identified via sequence -based typing of B-cell line no. 299 of the UCLA International Cell Exchange.

In this paper we report the identification of a new HLA-B allele in a sample that was distributed in the International UCLA Terasaki Cell/DNA Exchange, and the results were summarized in the final report of the 280th Cell Exchange. This novel allele officially designed B*3809 was found in B-cell line no. 299 from a Dutch Caucasoid donor and differs from B*3801 by mutation C-->G at position 483 in exon 3, resulting in an amino-acid substitution at codon 161 from aspartic acid in B*3801 to glutamic acid in B*3809, respectively.

Novel HLA-Cw*03 allele, Cw*030303, identified by nucleotide sequencing.

In this paper we report the identification of a new HLA- Cw*03 allele in a sample that has been distributed in the International UCLA Terasaki Cell/DNA Exchange. This novel allele officially designed Cw*03033 and renumbered to Cw*030303 (2) found in cell no. 1054 from an Asian Indian donor differs from Cw*030301 by a silent substitution at codon 128, GGG-->GGA (nucleotide position 384). This new allelic variant was confirmed by several other laboratories participating in the UCLA Terasaki Cell/DNA Exchange (3).

Sequence-based typing identifies a novel HLA-DPB1 allele, DPB1*9601.

In this report we describe the identification of a novel HLA-DPB1 allele, DPB1*9601, found in a Caucasian individual sample named ucla#356. The new allele was detected in the DNA of ucla#356 during routine HLA sequence-based typing (SBT) of samples participating in the UCLA International HLA DNA Exchange (number 55) for HLA DNA Proficiency Testing. DPB1*9601 was identical to DPB1*3901 except for a single nucleotide substitution 'G'-->'C' in previously constant position 277 (position 177, respectively, counting only exon 2). This nucleotide change causes an amino acid substitution from aspartic acid in DPB1*3901 to histidine at codon 64 in the novel allele. This new allele has been submitted to the EMBL database and has been assigned the accession number AJ514871. The WHO Nomenclature Committee has officially assigned the name DPB1*9601.

Differential peptide binding motif for three juvenile arthritis associated HLA-DQ molecules.

OBJECTIVE: In the oligoarticular subgroup of juvenile idiopathic arthritis, a strong association has been found with the expression of human leukocyte antigen class II molecules HLA-DQA1 *0401-DQB1*0402 and DQA1*0501-DQB1*0301, whereas DQA1*0501-DQB1*0201 is neutral and DQA1 *0201-DQB1*0201 protective. A presentation of different peptides by these DQ alleles would support their role in the disease process. METHODS: Using a synthetic nonapeptide library, a peptide binding motif was determined for the associated DQA1*0501-DQB1*0301 molecule and compared to the neutral and the protective DQ molecules. RESULTS: A differential motif for the three molecules could be deduced, suggesting that peptides preferentially binding to the associated vs. the neutral/protective DQ-molecules are mutually exclusive. CONCLUSION: These results imply a role for differential peptide presentation in the pathogenesis of oligoarthritic JIA. The search for peptides initiating the disease process might be facilitated which could then lead to therapeutical interventions.

Linkage disequilibria between HLA-B, C1_4_1, MICA and MICB.

The polymorphisms of MICA exon 5 (5 alleles), MICB intron 1 (13 alleles), C1_4_1 (6 alleles), HLA-B (29 alleles) and HLA-A (15 alleles) were investigated in a healthy German population. Sequencing was performed for the MICB alleles CA14, CA15, CA17, CA23 and CA26 isolated from different cell lines. Variation to the published sequence was observed for CA14, CA15 and for CA17. At the C1_4_1 locus a new allele (CAAA)9 was identified and confirmed by sequencing. Linkage disequilibria were investigated for two-point- and three-point-haplotypes. Although the average relative delta value correlates loosely with the physical distance from HLA-B to MICB: HLA-B-C1_4_1>HLA-B-MICA>HLA-B-MICB, there are several exceptions to this rule. Analyzing three-point-haplotypes for the segment MICB to HLA-A a wide variation of linkage disequilibria for some of the classical HLA-A, B haplotypes has been observed. While the HLA-A1, B8 haplotype displays strong relative delta values over the entire distance from HLA-A to MICB, other haplotypes have linkage disequilibria only in a limited region.