Engagement of MHC class I-specific inhibitory receptors regulates natural killer (NK) cell development and function. Using both new and previously characterized anti-Ly49 monoclonal antibodies, we comprehensively determined expression and co-expression frequencies of four Ly49 receptors by NK cells from MHC-congenic, MHC class I-deficient, and Ly49A-transgenic mice to study mechanisms that shap...

Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency disease characterized by abnormality of MHC class II molecules surface expression on peripheral blood lymphocytes and monocytes. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections but the immunodeficiency is not as severe as SCID (severe combined immunodeficien...

T cell recognition of peptide-MHC is highly specific and is sensitive to very low levels of agonist peptide; however, it is unclear how this effect is achieved or regulated. In this study we show that clustering class I MHC molecules on the cell surface of B lymphoblasts enhances their recognition by mouse and human T cells. We increased clustering of MHC I molecules by two methods, cholesterol...

Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation. We found that not only IFN-induced but also normal basal expression of MHC I required IFN receptors and signal transducer and activator of transcription (STAT)1, providing genetic evidence for continuous IFN signaling. Surprisingly, an IFN-independent ...

Neurons in the murine vomeronasal organ (VNO) express a family of class Ib major histocompatibility complex (MHC) proteins (M10s) that interact with the V2R class of VNO receptors. This interaction may play a direct role in the detection of pheromonal cues that initiate reproductive and territorial behaviors. The crystal structure of M10.5, an M10 family member, is similar to that of classical ...

Mouse NK cells express Ly-49 receptors specific for classical MHC class I molecules. Several of the Ly-49 receptors have been characterized in terms of function and ligand specificity. However, the only Ly-49 receptor-ligand interaction previously described in detail is that between Ly-49A and H-2D(d), as studied by point mutations in the ligand and the crystal structure of the co-complex of th...

MHC molecules associated with autoimmunity possess known structural features that limit the repertoire of peptides that they can present. Such limitation gives a selective advantage to TCRs that rely on interaction with the MHC itself, rather than with the peptide residues. At the same time, negative selection is impaired because of the lack of negatively selecting peptide ligands. The combinat...

Simian virus 40 (SV40) has been shown to enter mammalian cells via uncoated plasma membrane invaginations. Viral particles subsequently appear within the endoplasmic reticulum. In the present study, we have examined the surface binding and internalization of SV40 by immunoelectron microscopy. We show that SV40 associates with surface pits which have the characteristics of caveolae and are label...