OGT (-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.

The gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in cause over 12 diseases ('laminopathies'). Lamins A and C are identical for their first 566 residues.

Rapid analysis of forensic-related samples using two ambient ionization techniques coupled to high-resolution mass spectrometers.

Rationale: This paper highlights the versatility of interfacing two ambient ionization techniques, Laser Diode Thermal Desorption (LDTD) and Atmospheric Solids Analysis Probe (ASAP), to high-resolution mass spectrometers and demonstrate the method's capability to rapidly generate high-quality data from multiple sample types with minimal, if any, sample preparation.

Methods: For ASAP-MS analysis of solid and liquid samples, the material was transferred to a capillary surface before being introduced into the mass spectrometer. For LDTD-MS analysis, samples were solvent extracted, spotted in a 96-well plate, and the solvent was evaporated before being introduced into the mass spectrometer.

Characterization of the peptide binding specificity of the HLA class I alleles B*38:01 and B*39:06.

B*38:01 and B*39:06 are present with phenotypic frequencies <2% in the general population, but are of interest as B*39:06 is the B allele most associated with type 1 diabetes susceptibility and 38:01 is most protective. A previous study derived putative main anchor motifs for both alleles based on peptide elution data. The present study has utilized panels of single amino acid substitution peptide libraries to derive detailed quantitative motifs accounting for both primary and secondary influences on peptide binding.

The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires.

Here we describe a detailed quantitative peptide-binding motif for the common equine leukocyte antigen (ELA) class I allele Eqca-1*00101, present in roughly 25 % of Thoroughbred horses. We determined a preliminary binding motif by sequencing endogenously bound ligands. Subsequently, a positional scanning combinatorial library (PSCL) was used to further characterize binding specificity and derive a quantitative motif involving aspartic acid in position 2 and hydrophobic residues at the C-terminus.

Acyclovir Has Low but Detectable Influence on HLA-B*57:01 Specificity without Inducing Hypersensitivity.

Immune mediated adverse drug reactions (IM-ADRs) remain a significant source of patient morbidity that have more recently been shown to be associated with specific class I and/or II human leukocyte antigen (HLA) alleles. Abacavir-induced hypersensitivity syndrome is a CD8+ T cell dependent IM-ADR that is exclusively mediated by HLA-B*57:01. We and others have previously shown that abacavir can occupy the floor of the peptide binding groove of HLA-B*57:01 molecules, increasing the affinity of certain self peptides resulting in an altered peptide-binding repertoire.

Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles.

Chinese rhesus macaques are of particular interest in simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) research as these animals have prolonged kinetics of disease progression to acquired immunodeficiency syndrome (AIDS), compared to their Indian counterparts, suggesting that they may be a better model for HIV. Nevertheless, the specific mechanism(s) accounting for these kinetics remains unclear. The study of major histocompatibility complex (MHC) molecules, including their MHC/peptide-binding motifs, provides valuable information for measuring cellular immune responses and deciphering outcomes of infection and vaccine efficacy.

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire.

Idiosyncratic adverse drug reactions are unpredictable, dose-independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkages between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01.

Identification of the peptide-binding motif recognized by the pigtail macaque class I MHC molecule Mane-A1*082:01 (Mane A*0301).

Rhesus and pigtail macaques have proven to be valuable animal models for several important human diseases, including HIV, where they exhibit similar pathology and disease progression. Because rhesus macaques have been extensively characterized in terms of their major histocompatibility complex (MHC) class I alleles, their demand has soared, making them increasingly difficult to obtain for research purposes. This problem has been exacerbated by a continued export ban in place since 1978.