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: Antigen & T cell. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.

Patellofemoral Instability: A Consensus Statement From the AOSSM/PFF Patellofemoral Instability Workshop.

Abstract: To come to some consensus on the state of knowledge and opinion regarding the definitions of patellofemoral stability and instability, the clinical evaluation of patients with suspected patellar instability, treatment recommendations, and future directions of study on this subject, a workshop was jointly funded by the American Orthopedic Society for Sports Medicine (AOSSM) and the Patellofemoral Foundation (PFF), a nonprofit corporation with a mission to improve the care of patients with anterior knee problems through targeted research and education. Sixteen individuals with recognized expertise and experience from the fields of orthopaedic surgery, physical therapy, and basic science were invited to participate.

A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE

Abstract: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis. Immunization of B10.PL mice with the Ac1–9 peptide, the immunodominant determinant of myelin basic protein (MBP), produced a single episode of EAE followed by recovery and resistance to reinduction of disease. Using the CDR3 length spectratyping technique, we characterized the clonal composition of the Ac1–9–specific T cell repertoire from induction through onset and resolution of disease. Two clonally restricted subsets within a heterogeneous self-reactive repertoire were found in mouse lymph nodes, spleen, and spinal cord soon after immunization, before any sign of EAE. These clonotypes, designated BV8S2/BJ2S7 and BV16/BJ2S5, were present in all mice examined and thus considered public. BV8S2/BJ2S7 was found in far greater excess; was exclusively Th1 polarized; disappeared from the spinal cord, spleen, and lymph nodes concomitantly with recovery; and transferred disease to naive recipients. In contrast, BV16/BJ2S5 and numerous private clonotypes were either Th1 or Th2 and persisted following recovery. These results are consistent with the hypothesis that the public clonotype BV8S2/BJ2S7 is a driver of disease and necessary for its propagation.

Minimal peptide length requirements for CD4+ T cell clones - implications for molecular mimicry and T cell survival

Abstract: CD4 T lymphocytes usually recognize peptides of 12–16 amino acids in the context of HLA class II molecules. We have recently used synthetic peptide combinatorial libraries to dissect in detail antigen recognition by autoreactive CD4 T cell clones (TCC). The results of these studies demonstrated that antigen recognition by T cells is highly degenerate and that many cross-reactive ligands can be defined, some of which much more potent than the selecting autoantigen. Based on these observations, we examined the response of a myelin basic protein-specific HLA class II-restricted CD4 TCC to truncation variants of optimal ligands. Surprisingly, pentapeptides, tetrapeptides and even tripeptides derived from different segments of the optimal ligands were recognized by the TCC, and some were even more potent than the selecting autoantigen. In addition, these peptides enhanced the survival of the TCC at low concentration. The relevance of this finding was supported by the generation of pentapeptide-specific CD4 TCC from peripheral blood lymphocytes. These observations not only change existing views on the length requirements for activation of CD4 HLA class II-restricted T cells, but also extend our knowledge about the flexibility of TCR recognition and the potential for cross-reactivity in the immune system.

Structure–activity relationships of benzimidazole derivatives as antiparasitic agents: Dual activity-difference (DAD) maps

Abstract: Parasitic infections still remain a major health threat in developing countries. Herein we report a systematic characterization of the structure–activity relationships (SAR) of a comprehensive set of benzimidazole derivatives tested against Trichomonas vaginalis and Giardia intestinalis. The analysis was based on pairwise comparisons of the activity similarity and molecular similarity using different molecular representations. Overall, results encourage simultaneous lead optimization efforts for benzimidazole derivatives active against both protozoan. In order to explore the activity profile of the benzimidazoles against the two parasites, we developed the dual activity-difference (DAD) map. DAD map is a complementary approach to systematically characterize the SAR of compound data sets.