The Weak Energy Condition and the Expansion History of the Universe

We examine flat models containing a dark matter component and an arbitrary dark energy component, subject only to the constraint that the dark energy satisfies the weak energy condition. We determine the constraints that these conditions place on the evolution of the Hubble parameter with redshift, H(z), and on the scaling of the coordinate distance with redshift, r(z). Observational constraints on H(z) are used to derive an upper bound on the current matter density. We demonstrate how the weak energy condition constrains fitting functions for r(z).Comment: 5 pages, 3 figures, references and discussion adde

PAKC: a novel panel of HLA class I antigen presentation machinery knockout cells from the same genetic origin

A single model system for integrative studies on multiple facets of antigen presentation is lacking. PAKC is a novel panel of ten cell lines knocked out for individual components of the HLA class I antigen presentation pathway. PAKC will accelerate HLA-I research in the fields of oncology, infectiology, and autoimmunity.Proteomic

The SPPL3-defined glycosphingolipid repertoire orchestrates HLA class I-mediated immune responses (vol 54, 132.e1, 2021)

Chemical Immunolog

The SPPL3-defined glycosphingolipid repertoire orchestrates HLA class I-mediated immune responses

HLA class I (HLA-I) glycoproteins drive immune responses by presenting antigens to cognate CD8+ T cells. This process is often hijacked by tumors and pathogens for immune evasion. Because options for restoring HLA-I antigen presentation are limited, we aimed to identify druggable HLA-I pathway targets. Using iterative genome-wide screens, we uncovered that the cell surface glycosphingolipid (GSL) repertoire determines effective HLA-I antigen presentation. We show that absence of the protease SPPL3 augmented B3GNT5 enzyme activity, resulting in upregulation of surface neolacto-series GSLs. These GSLs sterically impeded antibody and receptor interactions with HLA-I and diminished CD8+ T cell activation. Furthermore, a disturbed SPPL3-B3GNT5 pathway in glioma correlated with decreased patient survival. We show that the immunomodulatory effect could be reversed through GSL synthesis inhibition using clinically approved drugs. Overall, our study identifies a GSL signature that inhibits immune recognition and represents a potential therapeutic target in cancer, infection, and autoimmunity.Bio-organic Synthesi