Gag protein epitopes recognized by ELA-A-restricted cytotoxic T lymphocytes from horses with long-term equine infectious anemia virus infection.
Abstract: Most equine infectious anemia virus (EIAV)-infected horses have acute clinical disease, but they eventually control the disease and become lifelong carriers. Cytotoxic T lymphocytes (CTL) are considered an important immune component in the control of infections with lentiviruses including EIAV, but definitive evidence for CTL in the control of disease in carrier horses is lacking. By using retroviral vector-transduced target cells expressing different Gag proteins and overlapping synthetic peptides of 16 to 25 amino acids, peptides containing at least 12 Gag CTL epitopes recognized by virus-stimulated PBMC from six long-term EIAV-infected horses were identified. All identified peptides were located within Gag matrix (p15) and capsid (p26) proteins, as no killing of target cells expressing p11 and p9 occurred. Each of the six horses had CTL recognizing at least one Gag epitope, while CTL from one horse recognized at least eight different Gag epitopes. None of the identified peptides were recognized by CTL from all six horses. Two nonamer peptide epitopes were defined from Gag p26; one (18a) was likely restricted by class I equine leukocyte alloantigen A5.1 (ELA-A5.1) molecules, and the other (28b-1) was likely restricted by ELA-A9 molecules. Sensitization of equine kidney target cells for CTLm killing required 10 nM peptide 18a and 1 nM 28b-1. The results demonstrated that diverse CTL responses against Gag epitopes were generated in long-term EIAV-infected horses and indicated that ELA-A class I molecules were responsible for the diversity of CTL epitopes recognized. This information indicates that multiple epitopes or whole proteins will be needed to induce CTL in horses with different ELA-A alleles in order to evaluate their role in controlling EIAV.
Publication Date: 1998-11-13 PubMed ID: 9811694PubMed Central: PMC110470DOI: 10.1128/JVI.72.12.9612-9620.1998Google Scholar: Lookup
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Summary
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The research article discusses a study that identified distinct protein fragments, or ‘epitopes’, of the equine infectious anemia virus (EIAV) recognized by the immune cells of long-term EIAV-infected horses, providing insights into the diverse immune response against EIAV and potential strategies for disease control.
Introduction to Equine Infectious Anemia Virus and the Body’s Immune Response
- The equine infectious anemia virus (EIAV) typically causes acute clinical disease in horses, but eventually, the horse’s immune system finds a way to control the disease, turning them into lifelong carriers.
- Cytotoxic T lymphocytes (CTLs), a type of immune cell, are believed to play a crucial role in controlling EIAV infection.
- However, concrete evidence of the role of CTLs in controlling EIAV infection in horses that become long-term carriers of the virus is lacking.
Methodology and Key Findings of the Study
- To provide more insight, the researchers used cells modified by a retroviral vector to express different Gag proteins—building blocks of the EIAV—and overlapping synthetic peptides, or smaller fragments of the protein.
- This study identified 12 distinct Gag CTL epitopes recognized by virus-stimulated PBMC (peripheral blood mononuclear cells) from six long-term EIAV-infected horses.
- All identified epitopes were located within matrix (p15) and capsid (p26) proteins of the virus, while none was found in two other proteins (p11 and p9) studied.
- Interestingly, each individual horse’s CTLs recognized at least one specific Gag epitope, showcasing the unique immune responses to the virus among different horses.
- Among these epitopes, two were likely associated with specific equine leukocyte alloantigen A (ELA-A) molecules, proteins that play a crucial role in the horse’s immune response.
Implications of the Findings
- These findings underscore the diversity of the immune response in horses against EIAV, suggesting that different ELA-A class I molecules could be responsible for recognizing and responding to different epitopes.
- This diversity indicates that to assess the role of CTLs in controlling EIAV (in different horses, corresponding to different ELA-A molecules), we’ll need to consider multiple epitopes or whole proteins.
- This line of research could pave the way for more effective therapeutic strategies controlling EIAV and potentially other similar viral infections.
Cite This Article
APA
Zhang W, Lonning SM, McGuire TC.
(1998).
Gag protein epitopes recognized by ELA-A-restricted cytotoxic T lymphocytes from horses with long-term equine infectious anemia virus infection.
J Virol, 72(12), 9612-9620.
https://doi.org/10.1128/JVI.72.12.9612-9620.1998 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040, USA.
MeSH Terms
- Amino Acid Sequence
- Animals
- Antigens, Viral / genetics
- Base Sequence
- Cell Line
- DNA Primers / genetics
- Epitope Mapping
- Epitopes, T-Lymphocyte / genetics
- Equine Infectious Anemia / immunology
- Equine Infectious Anemia / virology
- Gene Products, gag / genetics
- Gene Products, gag / immunology
- Genes, Viral
- Genetic Vectors
- Histocompatibility Antigens Class I
- Horses
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / immunology
- Infectious Anemia Virus, Equine / pathogenicity
- Molecular Sequence Data
- Peptide Fragments / genetics
- Peptide Fragments / immunology
- Retroviridae / genetics
- T-Lymphocytes, Cytotoxic / immunology
- Transduction, Genetic
Grant Funding
- AI-24291 / NIAID NIH HHS
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