Immunodominant surface epitopes power immune evasion in the African trypanosome.

The African trypanosome survives the immune response of its mammalian host by antigenic variation of its major surface antigen (the variant surface glycoprotein or VSG). Here we describe the antibody repertoires elicited by different VSGs. We show that the repertoires are highly restricted and are directed predominantly to distinct epitopes on the surface of the VSGs.

Analysis of the phosphoproteome of CK2/Δ C2C12 myoblasts compared to the wild-type cells.

CK2 is a Ser/Thr protein kinase composed of two catalytic (/') subunits and a non-catalytic β-subunit dimer, whose activity is often abnormally high in cancer cells. The concept that CK2 may be dispensable for cell survival has been challenged by the finding that viable CK2/' knock-out myoblast clones still express small amounts of an N-terminally deleted ' subunit generated during the CRISPR/Cas9 procedure. Here we show that, although the overall CK2 activity of these CK2/Δ' (KO) cells is less than 10% compared to wild-type (WT) cells, the number of phosphosites with the CK2 consensus is comparable to that of WT cells.

Comparing the efficacy and selectivity of Ck2 inhibitors. A phosphoproteomics approach.

CK2 (an acronym derived from the misnomer "casein kinase 2") denotes a ubiquitous, highly pleiotropic protein kinase which has been implicated in global human pathologies, with special reference to cancer. A large spectrum of fairly selective, cell permeable CK2 inhibitors are available, one of which, CX4945 is already in clinical trials for the treatment of neoplasia. Another recently developed CK2 inhibitor, GO289, displays in vitro potency and selectivity comparable to CX4945.

Piperlongumine Acts as an Immunosuppressant by Exerting Prooxidative Effects in Human T Cells Resulting in Diminished T17 but Enhanced T Differentiation.

Piperlongumine (PL), a natural small molecule derived from the Linn plant, has received growing interest as a prooxidative drug with promising anticancer properties. Yet, the influence of PL on primary human T cells remained elusive. Knowledge of this is of crucial importance, however, since T cells in particular play a critical role in tumor control.

Performance Evaluation of MHC Class-I Binding Prediction Tools Based on an Experimentally Validated MHC-Peptide Binding Data Set.

Knowing whether a protein can be processed and the resulting peptides presented by major histocompatibility complex (MHC) is highly important for immunotherapy design. MHC ligands can be predicted by peptide-MHC class-I binding prediction algorithms. However, prediction performance differs considerably, depending on the selected algorithm, MHC class-I type, and peptide length.

A non-functional neoepitope specific CD8 T-cell response induced by tumor derived antigen exposure .

Cancer-associated mutations, mostly single nucleotide variations, can act as neoepitopes and prime targets for effective anti-cancer T-cell immunity. T cells recognizing cancer mutations are critical for the clinical activity of immune checkpoint blockade (ICB) and they are potent vaccine antigens. High frequencies of mutation-specific T cells are rarely spontaneously induced.

A Targeted LC-MS Strategy for Low-Abundant HLA Class-I-Presented Peptide Detection Identifies Novel Human Papillomavirus T-Cell Epitopes.

For rational design of therapeutic vaccines, detailed knowledge about target epitopes that are endogenously processed and truly presented on infected or transformed cells is essential. Many potential target epitopes (viral or mutation-derived), are presented at low abundance. Therefore, direct detection of these peptides remains a challenge.

Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.

Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus.

Analysis of Major Histocompatibility Complex-Bound HIV Peptides Identified from Various Cell Types Reveals Common Nested Peptides and Novel T Cell Responses.

Unlabelled: Despite the critical role of epitope presentation for immune recognition, we still lack a comprehensive definition of HIV peptides presented by HIV-infected cells. Here we identified 107 major histocompatibility complex (MHC)-bound HIV peptides directly from the surface of live HIV-transfected 293T cells, HIV-infected B cells, and primary CD4 T cells expressing a variety of HLAs. The majority of peptides were 8 to 12 amino acids (aa) long and mostly derived from Gag and Pol.