The human CD8β M-4 isoform dominant in effector memory T cells has distinct cytoplasmic motifs that confer unique properties.

The CD8 co-receptor influences T cell recognition and responses in both anti-tumor and anti-viral immunity. During evolution in the ancestor of humans and chimpanzees, the CD8B gene acquired two additional exons. As a result, in humans, there are four CD8β splice variants (M1 to M4) that differ in their cytoplasmic tails.

Induced clustered nanoconfinement of superparamagnetic iron oxide in biodegradable nanoparticles enhances transverse relaxivity for targeted theranostics.

Purpose: Combined therapeutic and diagnostic agents, "theranostics" are emerging valuable tools for noninvasive imaging and drug delivery. Here, we report on a solid biodegradable multifunctional nanoparticle that combines both features.

Methods: Poly(lactide-co-glycolide) nanoparticles were engineered to confine superparamagnetic iron oxide contrast for magnetic resonance imaging while enabling controlled drug delivery and targeting to specific cells.

Pathogen-associated molecular patterns on biomaterials: a paradigm for engineering new vaccines.

Vaccine development has progressed significantly and has moved from whole microorganisms to subunit vaccines that contain only their antigenic proteins. Subunit vaccines are often less immunogenic than whole pathogens; therefore, adjuvants must amplify the immune response, ideally establishing both innate and adaptive immunity. Incorporation of antigens into biomaterials, such as liposomes and polymers, can achieve a desired vaccine response.

The impact of nanoparticle ligand density on dendritic-cell targeted vaccines.

Dendritic-cell (DC) targeted antigen delivery systems hold promise for enhancing vaccine efficacy and delivery of therapeutics. However, it is not known how the number and density of targeting ligands on such systems may affect DC function and subsequent T cell response. We modified the surface of biodegradable nanoparticles loaded with antigen with different densities of the mAb to the DC lectin DEC-205 receptor and assessed changes in the cytokine response of DCs and T cells.

Application of nanotechnologies for improved immune response against infectious diseases in the developing world.

There is an urgent need for new strategies to combat infectious diseases in developing countries. Many pathogens have evolved to elude immunity and this has limited the utility of current therapies. Additionally, the emergence of co-infections and drug resistant pathogens has increased the need for advanced therapeutic and diagnostic strategies.

Complexes of two cohorts of CLIP peptides and HLA-DQ2 of the autoimmune DR3-DQ2 haplotype are poor substrates for HLA-DM.

Atypical invariant chain (Ii) CLIP fragments (CLIP2) have been found in association with HLA-DQ2 (DQ2) purified from cell lysates. We mapped the binding register of CLIP2 (Ii 96-104) to DQ2 and found proline at the P1 position, in contrast to the canonical CLIP1 (Ii 83-101) register with methionine at P1. CLIP1/2 peptides are the predominant peptide species, even for DQ2 from HLA-DM (DM)-expressing cells.

The relative energetic contributions of dominant P1 pocket versus hydrogen bonding interactions to peptide:class II stability: implications for the mechanism of DM function.

Peptides are bound to MHC class II molecules by an array of hydrogen bonds between conserved MHC class II protein side-chains and the peptide backbone and through interactions between MHC protein pockets and peptide side-chain anchors. The crystal structure of murine I-A(k) protein with peptide shows a network of electrostatic interactions with the P1 aspartic acid anchor and an arginine in the P1 pocket that are thought to constitute the major stabilizing interaction between peptide and MHC. In this paper, have explored the relative energetic contribution of this dominant P1 pocket interaction with that made by a genetically conserved hydrogen bond which is formed by the beta 81 histidine residue and the main chain of the bound peptide.