IPD—the Immuno Polymorphism Database

IPD-MHC

The MHC sequences of many different species have been reported (6–17), along with different nomenclature systems used in the naming and identification of new genes and alleles in each species (18). The sequences of the MHC from a number of different species are highly conserved between species (19). The nomenclature for MHC genes and alleles in species other than humans (20,21) and mice (22,23) has historically been overseen either informally by groups generating sequences, or by formal nomenclature committees set up by the International Society for Animal Genetics (ISAG) (24). This work is now overseen by the Comparative MHC Nomenclature Committee and is supported by ISAG and the Veterinary Immunology Committee of the International Union of Immunological Societies (25). By bringing the work of different nomenclature committees and the sequences of different species together, it is hoped to provide a central resource that will facilitate further research on the MHC of each species and on their comparison (26).

The first version of the IPD-MHC database involved the work of groups specializing in non-human primates (NHP) (16), canines (DLA) (12) and felines (FLA) (27) and incorporated all data previously available in the IMGT/MHC database (26). Since the first version, we have been able to add sequences from cattle (BoLA) (17), teleost fish (28), rats (RT1) (29), sheep (OLA) (15) and swine (SLA) (14). In 2012, the nomenclature used to describe the alleles of NHP was extensively revised and updated (16). This was accompanied by updating the IPD-MHC NHP section to complement the publication; IPD-MHC NHP currently contains >4000 alleles covering 47 species of Apes, Old World and New World Monkeys. The management of the sequences within IPD-MHC and the provision of an online submission tool have enabled these databases to grow, the number of sequences increasing by at least 10% each year, and the nomenclature to expand since the inclusion of a species within IPD. This has resulted in regular publications reporting updates or changes to the nomenclature (15–17,30).

IPD-KIR

The KIRs are members of the immunoglobulin super family formerly called killer-cell inhibitory receptors. KIRs have been shown to be highly polymorphic both at the allelic and haplotypic levels (31). They are composed of two or three Ig-domains, a transmembrane region and cytoplasmic tail, which can in turn be short (activatory) or long (inhibitory). The leukocyte receptor complex, which encodes KIR genes, has been shown to be polymorphic, polygenic and complex in a manner similar to the MHC. Because of the complexity in the KIR region and KIR sequences, a KIR Nomenclature Committee was established in 2002, to undertake the naming of human KIR allele sequences. The first KIR Nomenclature report was published in 2003 (32), which coincided with the first release of the IPD-KIR database. The number of officially named human KIR alleles has increased since the initial release, which contained 89 alleles. As of September 2012, there are >600 alleles, which code for >320 unique protein sequences.

A recent development on the IPD-KIR website is online tools to assist in the prediction of transplant outcome in an unrelated haematopoetic stem cell transplant based on the KIR content of the individuals involved. In 2008, a tool was added to the website to help predict NK cell alloreactivity based on the KIR ligands present in the patient and donor, as transplant strategies based on KIR-ligand mismatches had been shown to influence relapse, graft versus host disease and survival in patients with acute myeloid leukaemia (33). In 2010, with the goal of developing a donor selection strategy to improve transplant outcome, Cooley et al., (34) compared the contribution of KIR gene motifs with the clinical benefit conferred by donors with a particular haplotype. Donor KIR genotype influenced transplantation outcome for some forms of leukaemia, after a T-cell replete unrelated donor transplant. KIR genotyping several HLA-matched potential donors could substantially increase the frequency of transplants using unrelated donor grafts with favorable KIR gene content. To implement this strategy, the IPD-KIR database was asked to provide an online version of the algorithm described in the article, see Figure 2. The B-Content calculator (http://www.ebi.ac.uk/ipd/kir/donor_b_content.html) allows the user to enter the KIR genotypes for up to five prospective donors, and receive their B-Content assignments, and a prediction result of the effect of the KIR genotype on transplant outcome. To ensure only valid KIR genotypes are submitted, all genotypes submitted are compared with a list of predicted genotypes based on known KIR haplotypes. In addition, this list has been supplemented with a number of additional KIR genotypes that have been defined in routine KIR typing. If a prospective donor's KIR typing does not match any of the genotypes on this list, a warning is issued.

In addition to allelic polymorphism, there is haplotypic variability within the KIR region due to the different number and kind of KIR genes. Haplotypic diversity is a major contributor to the population diversity of KIR and of cell repertoires. There are a number of fully sequenced KIR haplotypes that have been reported (35,36). The IPD-KIR website collates this data into a graphic displaying the gene and allele content of these, Figure 3. Where possible the alleles sequenced at the individual KIR genes are also listed. Some genes are only partially sequenced and for these an allele designation is not provided. The graphic provides interactive links to the individual allele entries, as well as details on the cell source used for each haplotype.

The IPD-KIR database is also being expanded to include the KIR sequences from other species, and most recently work has begun on including the sequences of KIR alleles found in Rhesus Macaques (Macaca mulatta) (37,38). Work is also underway on a number of other species of Macaques as well as Chimpanzees, Orangutans and Domestic Cattle (39–42). The non-human KIR sequences will be included into the IPD-KIR section and be accessible using the same tools as the human KIR sequences. Submission tools are already available for depositing non-human KIRs into the database.

IPD-HPA

Human platelet antigens (HPA) are alloantigens expressed only on platelets, specifically on platelet membrane glycoproteins. These platelet-specific antigens are immunogenic and can result in pathological reactions to transfusion therapy. The HPA nomenclature system was adopted in 1990 (43,44) to overcome problems with the previous nomenclature. Since then, more antigens have been described and the molecular basis of many has been resolved. As a result, the nomenclature was revised in 2003 (45) and included in the IPD project. The IPD-HPA section contains nomenclature information and additional background material. The different genes in the HPA system have not been sequenced to the same level as some of the other projects and so currently only single-nucleotide polymorphisms are used to determine alleles. This information is presented in a grid of single-nucleotide polymorphisms for each gene. The IPD and HPA nomenclature committee hope to expand this to provide full sequence alignments when possible.

IPD-ESTDAB

IPD-ESTDAB is a database of immunologically characterized melanoma cell lines. The database works in conjunction with the European Searchable Tumour Cell Line Database (ESTDAB) cell bank (46,47), which is housed in Tübingen, Germany and provides immunologically characterized tumour cells. The IPD-ESTDAB section of the website provides an online search facility for cells stored in this cell bank. This enables investigators to identify cells possessing specific parameters important for studies of immunity, immunogenetics, gene expression, metastasis, response to chemotherapy and other tumour biological experimentation. The search tool allows for searches based on a single parameter, or clusters of parameters on >250 different markers for each cell. The detailed reports produced can then be used to identify cells of interest, which can be obtained from the cell bank.