Immunogenetics

Maccari, Giuseppe; Robinson, James; Bontrop, Ronald; Otting, Nel; Groot, Natasja; Ho, Chak-Sum; Ballingall, Keith; Marsh, Steven; Hammond, John

doi: 10.1007/s00251-018-1072-4pmid: 30027299

The IPD-MHC Database is the official repository for non-human MHC sequences, overseen and supported by the Comparative MHC Nomenclature Committee, providing access to curated MHC data and associated analysis tools. To address the increasing amount and complexity of data being submitted, an entirely upgraded version of the IPD-MHC Database was recently released to maintain IPD-MHC as the central platform for the comparison of curated MHC data. As a consequence, a new level of nomenclature standardisation is required between the different species to enable data submission and to allow the unambiguous inter- and intra-species comparison of alleles. However, any changes must retain the flexibility demanded by the unique biology of different taxonomic groups. Here, we describe the rationale for a standardised nomenclature system and summarise the changes that have been driven by the requirements of implementing the IPD-MHC database. This modified nomenclature system is essential to maintain the current functionality of IPD-MHC and provide a scalable future-proof database organisation to fully exploit the bioinformatic tools used for analysis.

Ballingall, Keith; Bontrop, Ronald; Ellis, Shirley; Grimholt, Unni; Hammond, John; Ho, Chak-Sum; Kaufman, Jim; Kennedy, Lorna; Maccari, Giuseppe; Miller, Donald; Robinson, James; Marsh, Steven

doi: 10.1007/s00251-018-1073-3

Bardeskar, N.; Chavan, V.; Ahir-Bist, S.; Nanavati, R.; Samant-Mavani, P.; Mehta, P.; Mania-Pramanik, Jayanti

doi: 10.1007/s00251-018-1075-1pmid: 30128812

Human leukocyte antigen (HLA) molecules play a key role in regulating the immune response towards infectious agents like human immunodeficiency virus type-1 (HIV-1). They have been shown to influence transmission as well as the progression of HIV-1 towards acquired immune deficiency syndrome (AIDS). Roles of HLA-A and HLA-B have been documented extensively; however, HLA-C has been poorly studied. In the present study, we have evaluated the role of HLA-C in discordant couple and mother-to-child cohorts. HLA-C*07 was higher both in HIV-1-infected spouses and infants as compared to exposed uninfected spouses and infants. However, this was not significant. HLA-C*15 was significantly higher in HIV-1-exposed uninfected babies as compared to infected babies. Lack of treatment in mothers and breastfeeding were significantly associated with HIV-1 transmission. HLA-C*07 may be a susceptible allele in HIV-1 transmission, whereas HLA-C*15 may be a protective allele in mother-to-child cohorts, independent of feeding options and treatment. These findings could be important in targeting immune responses via population-specific vaccine strategies against HIV-1.

Abels, Wiebke; Manandhar, Trishna; Kunze-Schumacher, Heike; Blasczyk, Rainer; Bade-Döding, Christina

doi: 10.1007/s00251-018-1077-zpmid: 30128813

Peptide selection in infected cells is not fully understood yet, but several indications point to the fact that there are differences to uninfected cells, especially in productive HCMV infection, since HCMV evolved various strategies to disable the hosts immune system, including presentation of peptide-HLA complexes to immune effector cells. Therefore, peptide predictions for specific HLA alleles are limited in these cases and the naturally presented peptide repertoire of HCMV-infected cells is of major interest to optimize adoptive T cell therapies. The allotypes HLA-B*35:01 and B*35:08 differ at a single amino acid at position 156 and have been described to differ in their peptide features and in their association with the peptide loading complex. Virus specific T cells recognizing the allelic pHLA-B*35 complexes could be detected, indicating a significant role of this HLA subtypes in viral immunity. However, naturally selected and presented viral peptides have not been described so far. In this study, we analyzed the peptide binding repertoire for HLA-B*35:01 and HLA-B*35:08 in HCMV-infected cells. The isolated peptides from both allelic subtypes were of extraordinary length, however differed in their features, origin, and sequence. For these HCMV-originated peptides, no overlap in the peptide repertoire could be observed between the two allelic subtypes. These findings reveal the discrepancies between predicted and naturally presented immunogenic epitopes and support the need of comprehensive peptide recruitment data for personalized and effective cellular therapies.

Garrido, María; Rodriguez, Teresa; Zinchenko, Svitlana; Maleno, Isabel; Ruiz-Cabello, Francisco; Concha, Ángel; Olea, Nicolás; Garrido, Federico; Aptsiauri, Natalia

doi: 10.1007/s00251-018-1074-2pmid: 30145665

Schwartz, John; Hammond, John

doi: 10.1007/s00251-018-1067-1pmid: 29931472

The leukocyte receptor complex (LRC) encodes numerous immunoglobulin (Ig)-like receptors involved in innate immunity. These include the killer-cell Ig-like receptors (KIR) and the leukocyte Ig-like receptors (LILR) which can be polymorphic and vary greatly in number between species. Using the recent long-read genome assembly, Sscrofa11.1, we have characterized the porcine LRC on chromosome 6. We identified a ~ 197-kb region containing numerous LILR genes that were missing in previous assemblies. Out of 17 such LILR genes and fragments, six encode functional proteins, of which three are inhibitory and three are activating, while the majority of pseudogenes had the potential to encode activating receptors. Elsewhere in the LRC, between FCAR and GP6, we identified a novel gene that encodes two Ig-like domains and a long inhibitory intracellular tail. Comparison with two other porcine assemblies revealed a second, nearly identical, non-functional gene encoding a short intracellular tail with ambiguous function. These novel genes were found in a diverse range of mammalian species, including a pseudogene in humans, and typically consist of a single long-tailed receptor and a variable number of short-tailed receptors. Using porcine transcriptome data, both the novel inhibitory gene and the LILR were highly expressed in peripheral blood, while the single KIR gene, KIR2DL1, was either very poorly expressed or not at all. These observations are a prerequisite for improved understanding of immune cell functions in the pig and other species.

Fan, Shuhua; Wang, Yongli; Wang, Xian; Huang, Li; Zhang, Yunxia; Liu, Xiaomeng; Zhu, Wenshuai

doi: 10.1007/s00251-018-1070-6pmid: 29992375

In vitro refolding assays can be used to investigate the affinity and stability of the binding of epitope peptides to major histocompatibility complex (MHC) class I molecules, which are key factors in the presentation of peptides to cytotoxic T lymphocytes (CTLs). The recognition of peptide epitopes by CTLs is crucial for protection against influenza A virus (IAV) infection. The peptide-binding motif of the swine SLA-3*hs0202 molecule has been previously reported and partly overlaps with the binding motif of the most abundant human MHC allele, HLA-A*0201. In this study, we screened all the protein sequences of the swine-origin epidemic IAV strain A/Beijing/01/2009 (H1N1), and a total of 73 9-mer epitope peptides were predicted to fit the consensus motif of the swine SLA-3*hs0202 or HLA-A*0201 molecule. Then, 14 peptides were selected, and their affinities to SLA-3*hs0202 were tested by a modified in vitro refolding assay. Our results show that ten epitopes could tolerate gel filtration, indicating that these epitopes formed stable or partly stable complexes with SLA-3*hs0202. Eight out of the ten epitopes have been previously reported as HLA-A2-restricted epitopes, which implied cross-reactivity between swine and human MHC I specificities. Furthermore, the modified mini-system refolding method could be applied for the screening of peptides because the refolding efficiency remained almost unchanged with the positive peptide (HA-KMN9) subjected to size-exclusion chromatography and Resource Q anion-exchange chromatography. The results presented here provide new insight into the development of epitope-based vaccines to control IAV and increase our understanding of swine molecular immunology.

Lopes-Marques, Mónica; Machado, André; Barbosa, Susana; Fonseca, Miguel; Ruivo, Raquel; Castro, L.

doi: 10.1007/s00251-018-1071-5pmid: 29998404

The Cetacea infraorder comprises a very unique group within the mammalian lineage. While sharing common ancestors with terrestrial mammals, their exclusive dependence on aquatic environments makes them attractive models to explore the landscape of molecular shifts in radical habitat transitions. Among their diverse anatomical and physiological solutions, we find detectable genetic remodeling of the immune system. In agreement, here we show that the gene sequence of interleukin-20 (IL20) displays unambiguous signs of inactivation with several disruptive mutations, including stop codons, insertions, and a conserved trans-species mutation abolishing a canonical splice site, in nine analyzed cetacean genomes. Considering the suggested role of IL20 in skin immunity processes, including inflammation, epithelization, and remodeling, we propose that gene inactivation follows specific adaptations of cetacean skin to the aquatic environment, in frame with the less-is-more hypothesis.

Otting, Nel; Groot, Natasja; Bontrop, Ronald

doi: 10.1007/s00251-018-1089-8pmid: 30283990

The authors regret that an error was present in the Fig. 5 of the above article; some digits in the DRB allele-designations in Fig. 5 have been lost, and are incorrectly presented by only two digits. The correct allele-designations should have been four (or six) digits. The correct Figure is now presented correctly.

Kim, Taejoong; Hunt, Henry; Parcells, Mark; Santen, Vicky; Ewald, Sandra

doi: 10.1007/s00251-018-1069-zpmid: 29982918

The Figure 3 in the original version of this article was incorrectly published. In this article the top panel of Figure 3 that describes the amino acid sequence alignment is now added. The original article has been corrected.