Mapping and definition of HLA class I and II serologic epitopes using an unbiased reverse engineering strategy

Current models describing HLA epitopes are both theoretical and empirical. Each has limitations yielding discordant results and increasingly complex modeling. The models make a priori assumptions that epitopes must be present only on the mature protein, solvent accessible, on the ‘top’ (peptide binding surface) of the molecule, restricted to the same class as the antibody, and in the same position on the target allele if reactive to more than one locus. Results obtained counter to these assumptions are routinely discounted. For the 17th International Histocompatibility and Immunogenetics Workshop, we developed a reverse engineering algorithm to define epitopes without these assumptions on a cohort of 332 primary transplant pairs. Complete NGS typing of the transcribed (including leader) genomic DNA for 11 HLA loci of donor and recipient and DSA assignment by single antigen beads was performed. Our results show that, when grouped by 16 class I and II allele specific DSA, uniform clusters and 172 specific amino acid target epitopes are recognized by recipients despite originating from disparate HLA pairs. Data also show that these targets can be in the leader, alpha 3, transmembrane and cytoplasmic domains, thus calling into question current assumptions regarding immunogenic epitopes. Comparisons of amino acid epitopes defined by the Terasaki and Duquesnoy groups (TerEp and EpRegistry) are given.     

CD226 attenuates Treg suppressive capacity via CTLA-4 and TIGIT during EAE

The Cluster of differentiation 226(CD226)/T cell immunoglobulin and immune receptor tyrosine-based inhibitory motif domain (TIGIT) axis plays an important role in the balance of the immune response. A previous study showed that CD226 is involved in CD4+ T cell differentiation and that blocking CD226 may attenuate experimental autoimmune encephalomyelitis (EAE) development. However, the molecular mechanisms underlying this process remain incompletely understood. In this study, it was found that Cd226−/− mice were less susceptible to EAE and that there was less T helper 17(Th17) cell infiltration with higher levels of regulatory cells (Tregs) infiltration in the Cd226−/− EAE mouse central nervous system (CNS) compared with that in the WT EAE mouse CNS. Moreover, the suppressive function of Cd226−/− Tregs was upregulated compared with that of WT Tregs. Furthermore, it was observed that the expression levels of CTLA-4 and TIGIT on Cd226−/− Tregs were higher than those on WT Tregs during EAE in the spleen and CNS. Our results demonstrate a pivotal role for CD226 in attenuating Treg function in EAE that was associated with downregulating the expression levels of CTLA-4 and TIGIT.     

Correlations between TLR polymorphisms and inflammatory bowel disease: a meta-analysis of 49 case-control studies

Immunologic Research - Recently, the roles of toll-like receptor (TLR) polymorphisms in inflammatory bowel disease (IBD) were intensively explored, with conflicting results. Therefore, we performed...     

X-linked hyper-IgM syndrome complicated with interstitial pneumonia and liver injury: a new mutation locus in the CD40LG gene

Immunologic Research -     

Legionella feeleii: pneumonia or Pontiac fever? Bacterial virulence traits and host immune response

Medical Microbiology and Immunology - Gram-negative bacterium Legionella is able to proliferate intracellularly in mammalian host cells and amoeba, which became known in 1976 since they caused a...     

Identification and characterization of a novel natural recombinant avian leucosis virus from Chinese indigenous chicken flock

Virus Genes - Avian leukosis virus (ALV) caused tremendous economic losses to poultry industry all over the world, especially in China. One natural recombinant ALV strain, designated as HB2015032,...