GAD65 (524-543)

Product Name: GAD65 (524-543)

Sequence One Letter Code: SRLSKVAPVIKARMMEYGTT

Sequence Three Letter Code: H-Ser-Arg-Leu-Ser-Lys-Val-Ala-Pro-Val-Ile-Lys-Ala-Arg-Met-Met-Glu-Tyr-Gly-Thr-Thr-OH

Chemical Formula:C97H168N28O28S2

Molecular Weight: 2238.8

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Diabetes and Metabolic Syndrome

Source / Species: Human, mouse, rat

Conjugation: Unconjugated

Code Nacres: NA.26

Application: GAD65 (524–543) is a synthetic peptide derived from glutamic acid decarboxylase 65, a principal autoantigen implicated in type 1 diabetes. This epitope induces antigen-specific proliferative T cell responses in non-obese diabetic (NOD) mice and stimulates diabetogenic T cell clones, including BDC2.5. Immunization with this fragment enhances autoimmune susceptibility in adoptive transfer models, underscoring its pathogenic relevance. The peptide is broadly utilized to study autoreactive T cell activation, immune tolerance mechanisms, and β-cell–directed autoimmunity. It is a critical reagent in translational research examining antigen-specific immunotherapies and the immunopathogenesis of type 1 diabetes.

Current Research: Type 1 diabetes (T1D) is an autoimmune disorder characterized by the immune-mediated destruction of insulin-producing pancreatic β-cells. The disease is driven primarily by autoreactive T lymphocytes that recognize pancreatic antigens and initiate chronic inflammation within the islets of Langerhans. Among the autoantigens implicated in this process, glutamic acid decarboxylase 65 (GAD65) is one of the most extensively studied. GAD65 is an enzyme involved in the synthesis of the neurotransmitter γ-aminobutyric acid (GABA) and is highly expressed in pancreatic β-cells as well as neurons. Specific peptide epitopes derived from this protein, including GAD65 (524–543), have become valuable tools for investigating autoimmune responses associated with type 1 diabetes. Research using the GAD65 (524–543) peptide has provided important insights into the mechanisms of autoreactive T cell activation. In non-obese diabetic (NOD) mice—one of the most widely used animal models for T1D—this peptide acts as a potent antigen capable of stimulating antigen-specific CD4⁺ T cell responses. Studies have shown that T cells recognizing this epitope proliferate in response to peptide presentation by major histocompatibility complex (MHC) class II molecules. This antigen-specific activation triggers cytokine production and inflammatory signaling pathways that contribute to immune-mediated β-cell destruction. The peptide is also closely associated with the activity of diabetogenic T cell clones, including the well-characterized BDC2.5 T cell line, which recognizes pancreatic antigens and drives autoimmune pathology in NOD mice. Experimental stimulation with GAD65-derived epitopes enables researchers to study the activation thresholds, cytokine profiles, and migration patterns of these pathogenic T cells. Such investigations have been critical for understanding how autoreactive lymphocytes escape central and peripheral tolerance mechanisms and ultimately attack pancreatic tissue. Another major focus of current research involves the use of GAD65 peptides in adoptive transfer models of autoimmune diabetes. In these experiments, diabetogenic T cells are transferred into recipient animals to evaluate how antigen exposure influences disease progression. Immunization with peptides such as GAD65 (524–543) has been shown to increase autoimmune susceptibility in certain experimental settings, highlighting the pathogenic relevance of this epitope. These models provide controlled systems for examining how antigen presentation, costimulatory signals, and inflammatory mediators shape the development of autoimmune diabetes. Beyond studying disease mechanisms, the GAD65 (524–543) peptide is increasingly applied in research exploring antigen-specific immunotherapies. Because this epitope is recognized by diabetogenic T cells, it serves as a target for strategies aimed at inducing immune tolerance. Several experimental approaches are being investigated, including peptide-based tolerization, nanoparticle-mediated antigen delivery, and regulatory T cell–inducing therapies. The goal of these interventions is to selectively suppress pathogenic immune responses against β-cell antigens while preserving overall immune function. The peptide is also useful in immune monitoring and epitope mapping studies. By stimulating immune cells with defined peptide fragments, researchers can identify the specific antigenic determinants recognized by autoreactive T cells. This approach allows investigators to measure T cell proliferation, cytokine production, and activation markers using assays such as ELISPOT, flow cytometry, and proliferation assays. These studies help clarify how different epitopes contribute to disease progression and may reveal biomarkers associated with early autoimmune activity. Recent work has also examined how antigen presentation and immune regulation influence responses to GAD65 peptides. Dendritic cells and other antigen-presenting cells process and present GAD-derived epitopes to T cells, shaping the balance between inflammatory and regulatory immune responses. Understanding how these processes are regulated may help identify strategies to restore immune tolerance to β-cell antigens. In summary, GAD65 (524–543) is a widely used peptide reagent in type 1 diabetes research. Its ability to stimulate antigen-specific T cell responses in NOD mouse models makes it a powerful tool for investigating the mechanisms of β-cell autoimmunity. Through applications in T cell activation studies, adoptive transfer models, and experimental immunotherapies, this peptide continues to contribute to a deeper understanding of autoimmune diabetes and the development of targeted strategies aimed at preserving pancreatic β-cell function.