Immuno Polymorphism Database Research Articles

Full-resolution HLA and KIR gene annotations for human genome assemblies.

The human leukocyte antigen (HLA) genes and the killer cell immunoglobulin-like receptor (KIR) genes are critical to immune responses and are associated with many immune-related diseases. Located in highly polymorphic regions, it is difficult to study them with traditional short-read alignment-based methods. Although modern long-read assemblers can often assemble these genes, using existing tools to annotate HLA and KIR genes in these assemblies remains a nontrivial task. Here, we describe Immuannot, a new computation tool to annotate the gene structures of HLA and KIR genes and to type the allele of each gene. Applying Immuannot to 56 regional and 212 whole-genome assemblies from previous studies, we annotate 9931 HLA and KIR genes and found that almost half of these genes, 4068, have novel sequences compared with the current Immuno Polymorphism Database (IPD). These novel gene sequences are represented by 2664 distinct alleles, some of which contained nonsynonymous variations, resulting in 92 novel protein sequences. We demonstrate the complex haplotype structures at the two loci and report the linkage between HLA/KIR haplotypes and gene alleles. We anticipate that Immuannot will speed up the discovery of new HLA/KIR alleles and enable the association of HLA/KIR haplotype structures with clinical outcomes in the future.

A pan-cetacean MHC amplicon sequencing panel developed and evaluated in combination with genome assemblies.

The major histocompatibility complex (MHC) is a highly polymorphic gene family that is crucial in immunity, and its diversity can be effectively used as a fitness marker for populations. Despite this, MHC remains poorly characterised in non-model species (e.g., cetaceans: whales, dolphins and porpoises) as high gene copy number variation, especially in the fast-evolving class I region, makes analyses of genomic sequences difficult. To date, only small sections of class I and IIa genes have been used to assess functional diversity in cetacean populations. Here, we undertook a systematic characterisation of the MHC class I and IIa regions in available cetacean genomes. We extracted full-length gene sequences to design pan-cetacean primers that amplified the complete exon 2 from MHC class I and IIa genes in one combined sequencing panel. We validated this panel in 19 cetacean species and described 354 alleles for both classes. Furthermore, we identified likely assembly artefacts for many MHC class I assemblies based on the presence of class I genes in the amplicon data compared to missing genes from genomes. Finally, we investigated MHC diversity using the panel in 25 humpback and 30 southern right whales, including four paternity trios for humpback whales. This revealed copy-number variable class I haplotypes in humpback whales, which is likely a common phenomenon across cetaceans. These MHC alleles will form the basis for a cetacean branch of the Immuno-Polymorphism Database (IPD-MHC), a curated resource intended to aid in the systematic compilation of MHC alleles across several species, to support conservation initiatives.

Submitting Novel Full-Length HLA, MIC, and KIR Alleles with TypeLoader2.

The Immuno Polymorphism Database (IPD) plays a pivotal role for immunogenetics. Due to technical limitations, genotyping often focuses on specific key regions like the antigen recognition domain (ARD) for HLA genotyping, and the databases are populated accordingly. More recently, though, modern next generation sequencing (NGS) assays allow using larger gene segments or even complete genes for genotyping. It is therefore essential that the databases are updated with complete genetic reference sequences to fully serve current and future applications. However, the process of manually annotating and submitting full-length allele sequences to IPD is time-consuming and error-prone, which may discourage HLA-genotyping laboratories or researchers from submitting full-length sequences of novel alleles.Here, we detail the process of preparing and submitting novel HLA, MIC, and KIR alleles to ENA and IPD using TypeLoader2, a convenient software tool developed to streamline this process by automating the sequence annotation, the creation of all necessary files, as well as parts of the submission process itself. The software is freely available from GitHub ( https://github.com/DKMS-LSL/typeloader ).

Genetic assessment of BoLA-DRB3 polymorphisms by comparing Bangladesh, Ethiopian, and Korean cattle.

Attributable to their major function in pathogen recognition, the use of bovine leukocyte antigens (BoLA) as disease markers in immunological traits in cattle is well established. However, limited report exists on polymorphism of the BoLA gene in zebu cattle breeds by high resolution typing methods. Thus, we used a polymerase chain reaction sequence-based typing (PCR-SBT) method to sequence exon 2 of the BoLA class II DRB3 gene from 100 animals (Boran, n = 13; Sheko, n = 20; Fogera, n = 16; Horro, n = 19), Hanwoo cattle (n = 18) and Bangladesh Red Chittagong zebu (n = 14). Out of the 59 detected alleles, 43 were already deposited under the Immuno Polymorphism Database for major histocompatibility complex (IPD-MHC) while 16 were unique to this study. Assessment of the level of genetic variability at the population and sequence levels with genetic distance in the breeds considered in this study showed that Zebu breeds had a gene diversity score greater than 0.752, nucleotide diversity score greater than 0.152, and mean number of pairwise differences higher than 14, being very comparable to those investigated for other cattle breeds. Regarding neutrality tests analyzed, we investigated that all the breeds except Hanwoo had an excess number of alleles and could be expected from a recent population expansion or genetic hitchhiking. Howbeit, the observed heterozygosity was not significantly (p < 0.05) higher than the expected heterozygosity. The Hardy Weinberg equilibrium (HWE) analysis revealed non-significant excess of heterozygote animals, indicative of plausible over-dominant selection. The pairwise FST values suggested a low genetic variation among all the breeds (FST = 0.056; p < 0.05), besides the rooting from the evolutionary or domestication history of the cattle. No detached clade was observed in the evolutionary divergence study of the BoLA-DRB3 gene, inferred from the phylogenetic tree based on the maximum likelihood model. The investigation herein indicated the clear differences in BoLA-DRB3 gene variability between African and Asian cattle breeds.

Immunosuppression-enhancing effect of the administration of allogeneic canine adipose-derived mesenchymal stem cells (cA-MSCs) compared with autologous cA-MSCs in vitro

BackgroundRecently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable.ObjectivesTo investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient in vitro.MethodsCanine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization. For major DLA genotyping (DQA1, DQB1, and DRB1), peripheral blood mononuclear cells (PBMCs) from two dogs (Dogs 1 and 2) were analyzed by direct sequencing of polymerase chain reaction (PCR) products. The cA-MSCs were co-cultured at a 1:10 ratio with activated PBMCs (DLA matching or mismatching) for 3 days and analyzed for immunosuppressive (IDO, PTGS2, and PTGES), inflammatory (IL6 and IL10), and apoptotic genes (CASP8, BAX, TP53, and BCL2) by quantitative real-time reverse transcriptase-PCR.ResultscA-MSCs were expressed cell surface markers such as CD90+/44+/29+/45- and differentiated into osteocytes, chondrocytes, and adipocytes in vitro. According to the Immuno Polymorphism Database, DLA genotyping comparisons of Dogs 1 and 2 revealed complete differences in genes DQA1, DQB1, and DRB1. In the co-culturing of cA-MSCs and PBMCs, DLA mismatch between the two cell types induced a significant increase in the expression of immunosuppressive (IDO/PTGS2) and apoptotic (CASP8/BAX) genes.ConclusionsThe administration of cA-MSCs matching the recipient DLA type can alleviate the need to regulate excessive immunosuppressive responses associated with genes, such as IDO and PTGES. Furthermore, easy and reliable DLA genotyping technology is required because of the high degree of genetic polymorphisms of DQA1, DQB1, and DRB1 and the low readability of DLA 88.

MHCII3D-Robust Structure Based Prediction of MHC II Binding Peptides.

Knowledge of MHC II binding peptides is highly desired in immunological research, particularly in the context of cancer, autoimmune diseases, or allergies. The most successful prediction methods are based on machine learning methods trained on sequences of experimentally characterized binding peptides. Here, we describe a complementary approach called MHCII3D, which is based on structural scaffolds of MHC II-peptide complexes and statistical scoring functions (SSFs). The MHC II alleles reported in the Immuno Polymorphism Database are processed in a dedicated 3D-modeling pipeline providing a set of scaffold complexes for each distinct allotype sequence. Antigen protein sequences are threaded through the scaffolds and evaluated by optimized SSFs. We compared the predictive power of MHCII3D with different sequence-based machine learning methods. The Pearson correlation to experimentally determine IC50 values for MHC II Automated Server Benchmarks data sets from IEDB (Immune Epitope Database) is 0.42, which is in the competitor methods range. We show that MHCII3D is quite robust in leaving one molecule out tests and is therefore not prone to overfitting. Finally, we provide evidence that MHCII3D can complement the current sequence-based methods and help to identify problematic entries in IEDB. Scaffolds and MHCII3D executables can be freely downloaded from our web pages.

Nomenclature report for killer-cell immunoglobulin-like receptors (KIR) in macaque species: new genes/alleles, renaming recombinant entities and IPD-NHKIR updates.

The Killer-cell Immunoglobulin-like Receptors (KIR) are encoded by a diverse group of genes, which are characterized by allelic polymorphism, gene duplications, and recombinations, which may generate recombinant entities. The number of reported macaque KIR sequences is steadily increasing, and these data illustrate a gene system that may match or exceed the complexity of the human KIR cluster. This report lists the names of quality controlled and annotated KIR genes/alleles with all the relevant references for two different macaque species: rhesus and cynomolgus macaques. Numerous recombinant KIR genes in these species necessitate a revision of some of the earlier-published nomenclature guidelines. In addition, this report summarizes the latest information on the Immuno Polymorphism Database (IPD)-NHKIR Database, which contains annotated KIR sequences from four non-human primate species.

Nomenclature report on the major histocompatibility complex genes and alleles of the laboratory rat (Rattus norvegicus).

The laboratory rat (Rattus norvegicus) has a long tradition as experimental animal in transplantation and autoimmunity research and, hence, there has been an inherent interest in its major histocompatibility complex (MHC), the RT1 complex. Available inbred rat strains and their derived RT1-congenic and intra-RT1 recombinant congenic strains were crucial for definition and characterization of RT1 genes and alleles and essentially advanced elucidation of the RT1 genomic organization in the past. The Immuno Polymorphism Database (IPD) harbors a section for rat MHC genes and alleles (IPD-MHC RT1) since 2005. The curator for IPD-MHC RT1 provides official designations for newly described genes and alleles of RT1. This is the first nomenclature report of RT1 genes and alleles that are currently included in IPD-MHC RT1.

TypeLoader2: Automated submission of novel HLA and killer-cell immunoglobulin-like receptor alleles in full length.

The Immuno Polymorphism Database (IPD) databases provide global, curated repositories for information regarding polymorphisms of genes of the immune system, thereby generating immense value for the research and clinical communities. The advent of high‐throughput genotyping in immunogenetics has led to dramatically growing numbers of heretofore unknown HLA and lately also killer‐cell immunoglobulin‐like receptor (KIR) alleles, which are to be curated and deposited in the IPD‐IMGT/HLA and IPD‐KIR databases, respectively. It is highly desirable that these novel alleles are characterised and submitted in full length, and that known alleles are extended to cover the complete gene sequence.However, the manual annotation and submission of sequences to European Molecular Biology Laboratory's European Nucleotide Archive and the IPD‐IMGT/HLA and IPD‐KIR databases is time‐consuming and error‐prone. Here, we report the substantial extension of the HLA allele submission tool TypeLoader, which now also supports the annotation and submission of KIR alleles. To enable a more widespread use of this tool, we have made it available as a stand‐alone application that can easily be installed on standard Windows or Linux computers. Furthermore, an internal SQLite database was added to store a wide range of metadata about each allele. This allows TypeLoader2 to be used as a lab's central information platform for the annotation, curation and submission of full‐length HLA and KIR allele sequences. The software is freely available from GitHub (https://github.com/DKMS-LSL/typeloader).We hope that the increased convenience and scope of TypeLoader2 will foster the submission of more full‐length sequences to the IPD‐IMGT/HLA and IPD‐KIR databases, ultimately promoting the use of full‐length sequencing for genotyping both HLA and KIR.

Comparative MHC nomenclature: report from the ISAG/IUIS-VIC committee 2018.

Significant progress has been made over the last decade in defining major histocompatibility complex (MHC) diversity at the nucleotide, allele, haplotype, diplotype, and population levels in many non-human species. Much of this progress has been driven by the increased availability and reduced costs associated with nucleotide sequencing technologies. This report provides an update on the activities of the comparative MHC nomenclature committee which is a standing committee of both the International Society for Animal Genetics (ISAG) and the International Union of Immunological Societies (IUIS) where it operates under the umbrella of the Veterinary Immunology Committee (VIC). A previous report from this committee in 2006 defined the role of the committee in providing guidance in the development of a standardized nomenclature for genes and alleles at MHC loci in non-human species. It described the establishment of the Immuno Polymorphism Database, IPD-MHC, which continues to provide public access to high quality MHC sequence data across a range of species. In this report, guidelines for the continued development of a universal MHC nomenclature framework are described, summarizing the continued development of each species section within the IPD-MHC project.

The IPD Databases: Cataloguing and Understanding Allele Variants.

The IMGT/HLA Database has provided a repository for information regarding polymorphism in the genes of the immune system since 1998. In 2003, it was absorbed into the Immuno Polymorphism Database (IPD). The IPD project has enabled us to create and maintain a platform for curating and publishing locus-specific databases which are either involved directly with, or relate to, the function of the Major Histocompatibility Complex across a number of species. In collaboration with specialist groups and nomenclature committees individual sections have been curated prior to their submission to the IPD for online publication. The IPD consists of five core databases, with the primary database being the IMGT/HLA Database. With the work of various nomenclature committees, the HLA Informatics Group, and alongside the European Bioinformatics Institute, we provide access to this data through the website ( http://www.ebi.ac.uk/ipd/ ) to the public domain. The IPD project continually develops new tools in conjunction with on-going scientific developments-such as Next-Generation Sequencing-to maintain efficiency and usability in response to user feedback and requests. The website is updated on a regular basis to ensure that new and confirmatory sequences are distributed to the immunogenetics community, as well as the wider research and clinical communities.

Killer Cell Immunoglobulin-like Receptor Ligand Matching Determines the Post-Transplant High Risk Groups Among Patients with Permissive HLA Mismatch in Unrelated Donor Hematopoietic Cell Transplantation

Background: Human leukocyte antigen (HLA) matching between donor and recipient is a key part of successful allogeneic hematopoietic cell transplantation (allo-HCT). The HCT from the unrelated donor (UD) with one allele/antigen mismatch (MM) can be as beneficial as HCT from perfectly matched donor. For the remaining patients, the donors with permissive mismatches may be the option. In HLA-mismatched transplantation, the patient and donor can also be mismatched for their killer cell immunoglobulin-like receptor (KIR) ligands that recognize allotypic determinants shared by certain HLA class I allele groups. Recent research has accumulated evidence of the role of each HLA locus and KIR ligand MM on clinical outcomes for UD-HCT. However, HCT outcomes of the patients with permissive MM depending on KIR ligand MM (KIR-L-MM) status remain obscure in UD-HCT.In the current study, we identified permissive and nonpermissive MM allele combinations and analyzed the effects of these mismatches in combination of KIR ligand mismatches in patients with acute myeloid leukemia (AML).Methods: A total of 438 patients with AML who underwent allo-HCT from UD from 2007 to 2014 were analyzed. Alleles of patients and donors at the HLA-A, -B, -C, and -DRB1 loci were identified by the high resolution DNA typing. Nonpermissive HLA allele combinations were defined as a significant HLA risk factor for severe acute graft-versus-host disease (aGVHD). KIR-L-MM among patient-donor pairs were searched in the Immuno Polymorphism Database available at www.ebi.ac.uk/ipd/kir.Results: Median age of the patients was 45 (range 15-60) years and 117 patients (40.4%) were female. Eighty-five (19.4%) patients were high risk at the time of HCT. Reduced intensity conditioning was performed in 131 patients (29.9%) and anti-thymocyte globulin was used in 324 patients (74.0%). Primary graft source was peripheral blood stem cells (n=369, 84.2%) and median 6.0 x 106/kg cells were infused. Severe aGVDH occurred in 43 patients (9.8%) and chronic GVHD (cGVHD) in 193 (44.1%). With median follow-up duration of 19 (range, 2-96) months, treatment-related mortality (TRM) occurred in 111 patients (25.3%), relapse in 119 (27.2%) and death in 214 (48.9%).Two-hundred sixty-four patients (60.3%) were HLA full matched in the 4 loci. Mismatches in HLA-A loci observed in 64 patients, HLA-B in 35, HLA-C in 98, and HLA-DRB1 in 60. Five nonpermissive MM pairs in 33 patients were identified as donor/patient pair: A*02:06/A*02:01, C*03:03/C*08:01, C*08:01/C03:04, C*08:01/C*15:02, and DRB1*04:03/DRB1*04:05. Among 98 patients with HLA-C loci MM, 16 patients showed KIR ligand MM (KIR-L-MM) as GvH direction, which was observed in the permissive MM group.Severe aGVHD occurred in 30.4%, 22.4%, 13.4%, and 10.8% in nonpermissive, permissive MM and KIR-L-MM, permissive MM and KIR-L-M, and full match group, respectively (p=0.003). The 3-year overall survival (OS) rate was inferior in permissive MM and KIR-L-MM group (30.0%) compared to full match (53.5%), permissive MM and KIR-L-M (51.8%), and nonpermissive (42.4%) group (p=0.067). The 3-year TRM was higher in permissive MM and KIR-L-MM group (57.5%) than full match (21.0%), permissive MM and KIR-L-M (27.7%), and nonpermissive (33.3%) group (p=0.006). In the multivariate analysis, high risk at HCT (HR 2.087, p<0.001), severe aGVHD (HR 3.851, p<0.001), and cGVHD (HR 0.321, p<0.001) were identified as variables affecting the OS. The following variables adversely affected on TRM: permissive MM and KIR-L-MM group (HR 2.699, p=0.007), severe aGVDH (HR 2.204, p=0.001), and cGVHD (HR 2.052, p<0.001). Non-permissive MM (HR 7.487, p=0.001) and CD34+ cells >6x106/kg (HR 4.113, p=0.017) were high risk factors on severe aGVHD.Conclusion: Permissive MM for HLA could be further classified into high risk groups with regard to TRM by KIR-L matching in UD-HCT. The evaluation of KIR-L matching is warranted to reduce unfavorable outcomes among the patients with permissive MM in UD-HCT. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The IPD-IMGT/HLA Database – New developments in reporting HLA variation

IPD-IMGT/HLA is a constituent of the Immuno Polymorphism Database (IPD), which was developed to provide a centralised system for the study of polymorphism in genes of the immune system. The IPD project works with specialist groups of nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The primary database within the IPD project is the IPD-IMGT/HLA Database, which provides a locus-specific database for the hyper-polymorphic allele sequences of the genes in the HLA system, also known as the human Major Histocompatibility Complex. The IPD-IMGT/HLA Database was first released over 17years ago, building on the work of the WHO Nomenclature Committee for Factors of the HLA system that was initiated in 1968. The IPD-IMGT/HLA Database enhanced this work by providing the HLA community with an online, searchable repository of highly curated HLA sequences. Many of the genes encode proteins of the immune system and are hyper polymorphic, with some genes currently having over 4000 known allelic variants. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute we are able to provide public access to this data through the website, http://www.ebi.ac.uk/ipd/imgt/hla.

The IPD and IMGT/HLA database: allele variant databases.

The Immuno Polymorphism Database (IPD) was developed to provide a centralized system for the study of polymorphism in genes of the immune system. Through the IPD project we have established a central platform for the curation and publication of locus-specific databases involved either directly or related to the function of the Major Histocompatibility Complex in a number of different species. We have collaborated with specialist groups or nomenclature committees that curate the individual sections before they are submitted to IPD for online publication. IPD consists of five core databases, with the IMGT/HLA Database as the primary database. Through the work of the various nomenclature committees, the HLA Informatics Group and in collaboration with the European Bioinformatics Institute we are able to provide public access to this data through the website http://www.ebi.ac.uk/ipd/. The IPD project continues to develop with new tools being added to address scientific developments, such as Next Generation Sequencing, and to address user feedback and requests. Regular updates to the website ensure that new and confirmatory sequences are dispersed to the immunogenetics community, and the wider research and clinical communities.

IMGT/HLA and the Immuno Polymorphism Database.

The IMGT/HLA Database (http://www.ebi.ac.uk/ipd/imgt/hla/) was first released over 15 years ago, providing the HLA community with a searchable repository of highly curated HLA sequences. The HLA complex is located within the 6p21.3 region of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and are highly polymorphic, with some genes currently having over 3,000 known allelic variants. The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) expands on this model, with a further set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. IPD currently consists of four databases: IPD-KIR contains the allelic sequences of killer-cell immunoglobulin-like receptors; IPD-MHC is a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute we are able to provide public access to this data through the website http://www.ebi.ac.uk/ipd/.

IPD—the Immuno Polymorphism Database

The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project.

Bioinformatic Databases and Resources in the public domain to aid HLA research

Research in HLA as in any other field depends on information. Different groups have generated generic and specific resources and tools to support this research. The present review describes a qualified subset of these resources, which should cover the most important starting points for research in the HLA field. It discusses access to HLA allele sequences, allele frequencies, continues with general support to access to literature, DNA and protein sequence information, structural models, teaching books, databases with phenotypic datasets, alignment tools, peptide binding, statistical tools, guidelines and ambiguity coding. Following functionalities and databases have been included: IMGT/HLA, Immuno Polymorphism Database (IPD), allele frequencies*.net, a detailed look into NCBI (National Center of Biotechnology Information) with a subset of databases and tools, focusing on literature research, sequences, user-specific support tools and applications (PubMed, GenBank, MyNCBI, blast, Gene, MapViewer, Structure, CN3D, WorkBench, and dbMHC). This is followed by a brief survey of EBI-EMBL/Ensemble, the sequence alignment tool Clustal, the peptide and ligand databases SYFPEITHI and Immune Epitope Database, and last but not least statistical packages and HLA allele coding resources PyPop, the Immuno-genomics Data Analysis Working Group and the NMDP informatics section. All databases and tools can be freely accessed. Data linked to individuals, however, might require authorization by a data access committee.

Nomenclature report on the major histocompatibility complex genes and alleles of Great Ape, Old and New World monkey species

The major histocompatibility complex (MHC) plays a central role in the adaptive immune response. The MHC region is characterised by a high gene density, and most of these genes display considerable polymorphism. Next to humans, non-human primates (NHP) are well studied for their MHC. The present nomenclature report provides the scientific community with the latest nomenclature guidelines/rules and current implemented nomenclature revisions for Great Ape, Old and New World monkey species. All the currently published MHC data for the different Great Ape, Old and New World monkey species are archived at the Immuno Polymorphism Database (IPD)-MHC NHP database. The curators of the IPD-MHC NHP database are, in addition, responsible for providing official designations for newly detected polymorphisms.

Cattle MHC nomenclature: is it possible to assign sequences to discrete class I genes?

The cattle major histocompatibility complex (MHC) region contains a variable number of classical class I genes encoding polymorphic molecules involved in antigen presentation. Six classical class I genes have been described, but assigning sequences to these genes has proved problematic. We propose a refinement of the existing nomenclature, which currently names the 97 known classical class I sequences in a single series. Phylogenetic analysis of the 3' portion of the coding region allows segregation of these into six groups; thus, we have prefixed existing names with the appropriate number. Although it is clear that some of these groups correspond to discrete genes, it is currently not possible to state definitively that all do. However, the main groupings are consistent, and in conjunction with other evidence, we feel it is now appropriate to rename the sequences accordingly. Segregation of sequences into groups in this way will facilitate ongoing research and future use of the cattle MHC section of the Immuno Polymorphism Database.

Progress of the Comparative MHC Committee and a summary of the Comparative MHC Workshops held at the 32nd ISAG, Edinburgh and the 9th IVIS, Tokyo, 2010

The comparative MHC Nomenclature Committee was formed following a recommendation by the International Society for Animal Genetics (ISAG) at its meeting in Göttingen, Germany in 2002. The committee subsequently became affiliated to VIC, the Veterinary Immunology Committee of IUIS; the International Union of Immunological Societies, which is the umbrella organization for immunology societies worldwide. The committee currently fulfils three roles: (1) to establish guidelines for MHC nomenclature in species outside of human and mouse, (2) to facilitate the development of databases which provide a source of validated MHC sequences with official nomenclatures for associated species (immuno-polymorphism database IPD-MHC) and (3) to facilitate scientific discussion on comparative aspects of MHC biology. The committee currently comprises individuals representing a range of species nomenclature committees. This report summarises progress the committee has made in addressing its core objectives as well as the principal outputs from the Comparative MHC Workshops held at the 32nd International Society for Animal Genetics (ISAG) conference in Edinburgh, UK in July 2010 as well as in August 2010 at the 9th International Veterinary Immunology Symposium (IVIS) in Tokyo, Japan. Additional data from posters and presentations at related workshops focussing on aspects of MHC biology are also included where appropriate.