Lipopeptide stimulation of MHC class I-restricted memory cytotoxic T lymphocytes from equine infectious anemia virus-infected horses.
Abstract: The immunogenicity of equine infectious anemia virus (EIAV) Gag and Env equine leukocyte alloantigen (ELA)-A5.1, -A9, and -A1 restricted cytotoxic T lymphocyte (CTL) epitopes synthesized on multiple antigenic peptide (MAP) system coupled to tripalmitoyl-S-glycerylcysteine (P3C) was evaluated in vitro. P3C-MAP-peptide-stimulated peripheral blood mononuclear cells (PBMCs) from horses, chronically infected with EIAV, had memory CTL (CTLm) similar to that of PBMCs stimulated with either the minimal CTL epitopes, longer peptides containing the CTL epitopes, or EIAV. The stimulated CTL lysed EIAV-infected target cells and the percent specific lysis was dependent on the dose of P3C-MAP-peptide used to stimulate PBMCs in vitro and was peptide specific and ELA-A restricted. The results suggest that these P3C-MAP-peptides can be used as immunogens to stimulate primary immune responses in vivo.
Publication Date: 2002-03-22 PubMed ID: 11906769DOI: 10.1016/s0264-410x(01)00517-5Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The study investigates how certain synthetic peptides connected to a lipopeptide stimulate memory cytotoxic T lymphocytes in horses infected with equine infectious anemia virus (EIAV). The research suggests that these peptide combinations could be used as immunogens to kick-start primary immune responses in a living organism.
Background
- The study revolves around equine infectious anemia virus (EIAV), a retrovirus causing an often fatal disease in horses. The virus prompts the body’s immune cells to produce cytotoxic T lymphocytes (CTLs), which have a primary role in mediating antiviral responses.
- In this study, the team explored the immunogenic properties of specific EIAV proteins (Gag and Env) that are known to trigger the immune response in horses. They synthesized these proteins on a multiple antigenic peptide (MAP) system coupled to a lipopeptide called tripalmitoyl-S-glycerylcysteine (P3C).
Methods
- The team stimulated peripheral blood mononuclear cells (PBMCs) – white blood cells– from horses that were chronically infected with EIAV using their synthetic peptide-lipopeptide combination (P3C-MAP-peptide).
- They then measured the response of the CTLs using various strategies: comparing the PBMCs stimulated with the synthetic peptide, longer peptides containing CTL epitopes, or just EIAV.
Key Findings
- The stimulated CTLs were found to attack EIAV-infected target cells. Furthermore, the amount of destruction these cells caused was dependent on the dose of P3C-MAP-peptide that was used to initiate the reaction.
- The interaction was both peptide-specific and restricted to equine leukocyte alloantigen (ELA) -A, indicating that the P3C-MAP-peptides are promising candidates for stimulating primary immune responses in vivo.
Implications
- The implications of these findings suggest a potential breakthrough in the treatment and management of EIAV. Developing an effective treatment approach using the P3C-MAP peptides could be possible.
- This study sets the stage for further research into the applicability of these findings beyond EIAV, potentially offering implications for human immunodeficiency treatments as well.
Cite This Article
APA
Ridgely SL, McGuire TC.
(2002).
Lipopeptide stimulation of MHC class I-restricted memory cytotoxic T lymphocytes from equine infectious anemia virus-infected horses.
Vaccine, 20(13-14), 1809-1819.
https://doi.org/10.1016/s0264-410x(01)00517-5 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
MeSH Terms
- Amino Acid Sequence
- Animals
- Antigens, Viral / administration & dosage
- Antigens, Viral / genetics
- Cysteine / administration & dosage
- Cysteine / analogs & derivatives
- Cysteine / immunology
- Epitopes / administration & dosage
- Epitopes / genetics
- Equine Infectious Anemia / immunology
- Gene Products, env / administration & dosage
- Gene Products, env / genetics
- Gene Products, env / immunology
- Histocompatibility Antigens Class I / metabolism
- Horses
- Immunologic Memory
- In Vitro Techniques
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / immunology
- Lipoproteins / genetics
- Lipoproteins / immunology
- Lipoproteins / pharmacology
- Molecular Sequence Data
- T-Lymphocytes, Cytotoxic / drug effects
- T-Lymphocytes, Cytotoxic / immunology
- Viral Core Proteins / administration & dosage
- Viral Core Proteins / genetics
- Viral Core Proteins / immunology
Grant Funding
- AI01548 / NIAID NIH HHS
- AI24291 / NIAID NIH HHS
- K08 AI07025 / NIAID NIH HHS
Citations
This article has been cited 2 times.- Basto AP, Leitão A. Targeting TLR2 for vaccine development. J Immunol Res 2014;2014:619410.
- Mealey RH, Lee JH, Leib SR, Littke MH, McGuire TC. A single amino acid difference within the alpha-2 domain of two naturally occurring equine MHC class I molecules alters the recognition of Gag and Rev epitopes by equine infectious anemia virus-specific CTL. J Immunol 2006 Nov 15;177(10):7377-90.
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