Torrey Pines Institute for Molecular Studies

About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: T cell & Antigen. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.

Alzheimer's disease in a dish: promises and challenges of human stem cell models

Abstract: Human pluripotent stem cells can differentiate into disease-relevant cell types, which capture the unique genome of an individual patient and provide insight into pathological mechanisms of human disease. Recently, human stem cell models for Alzheimer's disease (AD), the most common neurodegenerative dementia, have been described. Stem cell-derived neurons from patients with familial and sporadic AD and Down's syndrome recapitulate human disease phenotypes such as amyloid β peptide production, hyperphosphorylation of tau protein and endosomal abnormalities. Treatment of human neurons with small molecules can modulate these phenotypes, demonstrating the utility of this system for drug development and screening. This review will highlight the current AD stem cell models and discuss the remaining challenges and potential future directions of this field.

Location of human cytotoxic T cell epitopes within a polymorphic domain of the Plasmodium falciparum circumsporozoite protein

Abstract: Studies in mice have shown that cytotoxic T lymphocytes (CTL) specific for epitopes within the circumsporozoite (CS) protein of malaria sporozoltes can prevent malaria probably by destroying infected hepatocytes. This has provided a model for the development of a sporozoite vaccine. It has not been shown whether humans can mount a CTL response to this protein nor what determinants on the protein could be considered as target epitopes for such cells and thus merit Inclusion in a sporozoite vaccine. We have used a novel technique to study a Caucasian population which would benefit from a sporozoite vaccine and have been able to demonstrate that some Individuals with a history of sporozoite exposure do contain peripheral blood CTL specific for the Plasmodium falciparum CS protein. The prevalence of CTL among different Individuals Is low and there is evidence that recent malaria exposure may be a prerequisite for finding such CTL. In three Individuals, CTL could be repeatedly found and in all cases the epttopes mapped to one of the two polymorphic C-terminal domains. Using a CTL line, we mapped a recognition site to residues 351 – 395 of the CS protein, overlapping the region of the protein recognized by murine CTL.

Redundancy in Antigen-Presenting Function of the HLA-DR and -DQ Molecules in the Multiple Sclerosis-Associated HLA-DR2 Haplotype

Abstract: The three HLA class II alleles of the DR2 haplotype, DRB1*1501, DRB5*0101, and DQB1*0602, are in strong linkage disequilibrium and confer most of the genetic risk to multiple sclerosis Functional redundancy in Ag presentation by these class II molecules would allow recognition by a single TCR of identical peptides with the different restriction elements, facilitating T cell activation and providing one explanation how a disease-associated HLA haplotype could be linked to a CD4+ T cell-mediated autoimmune disease Using combinatorial peptide libraries and B cell lines expressing single HLA-DR/DQ molecules, we show that two of five in vivo-expanded and likely disease-relevant, cross-reactive cerebrospinal fluid-infiltrating T cell clones use multiple disease-associated HLA class II molecules as restriction elements One of these T cell clones recognizes >30 identical foreign and human peptides using all DR and DQ molecules of the multiple sclerosis-associated DR2 haplotype A T cell signaling machinery tuned for efficient responses to weak ligands together with structural features of the TCR-HLA/peptide complex result in this promiscuous HLA class II restriction