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Immunology2002; 105(3); 295-305; doi: 10.1046/j.0019-2805.2001.01370.x

Identification of broadly recognized, T helper 1 lymphocyte epitopes in an equine lentivirus.

Abstract: Equine infectious anaemia virus (EIAV) is a horse lentivirus causing lifelong, persistent infection. During acute infection, CD8(+) cytotoxic T lymphocytes (CTL) are probably involved in terminating plasma viraemia. However, only a few EIAV CTL epitopes, restricted to fewer horse major histocompatibility complex (MHC) class I alleles, are known. As interferon-gamma (IFN-gamma)-secreting CD4(+), T helper 1 (Th1) lymphocytes promote CTL activity and help maintain memory CTL, identifying broadly recognized EIAV Th1 epitopes would contribute significantly to vaccine strategies seeking to promote strong CTL responses among horses with varying class I haplotypes. To this end, peripheral blood mononuclear cells (PBMC) from 10 MHC disparate, EIAV-infected horses were tested in T-lymphocyte proliferation assays for recognition of peptides from the Gag p26 capsid region and a portion of Pol. Both regions are highly conserved among EIAV isolates, and this Pol region is 51-63% homologous to other lentiviral Pol proteins. Seven of 10 horses recognized peptide Gag 221-245, and peptides Gag 242-261 and Pol 323-344 were recognized by five and four horses, respectively. Furthermore, the Gag peptides were recognized by two additional horses after resolving their initial plasma viraemia, indicating that these two peptides can be immunodominant early in infection. Gag peptide-responsive PBMC produced only IFN-gamma, indicating a Th1 response, while Pol 323-344-responsive PBMC produced IFN-gamma both with and without interleukin-4. PBMC from uninfected horses failed to either proliferate or secrete cytokines in response to peptide stimulation. Finally, CD4(+) T lymphocytes were required for proliferation responses, as shown by assays using CD4- versus CD8-depleted PBMC.
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Publication Date: 2002-03-29 PubMed ID: 11918691PubMed Central: PMC1782660DOI: 10.1046/j.0019-2805.2001.01370.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates certain immune responses in horses infected with equine infectious anaemia virus (EIAV). Specifically, it identifies certain proteins in the virus that are widely recognized by T helper 1 lymphocytes, a type of immune cells that aid in the activation and function of other immune cells.

Understanding EIAV and T-helper 1 Lymphocytes

  • The study focuses on the equine infectious anaemia virus, a lentivirus that causes persistent, lifelong infection in horses. One potent combating mechanism against this virus is the CD8(+) cytotoxic T lymphocytes (CTL), crucial immune cells that get rid of infected cells in the body.
  • However, CTL responses are specific and only recognize certain “epitopes” or fragments of the virus. So far, only a few EIAV epitopes known to be recognized by CTLs have been identified.
  • The research emphasizes the role of T-helper 1 (Th1) lymphocytes. These are a group of immune cells that produce specific signaling molecules such as interferon-gamma (IFN-gamma). This molecule guides CTL activity and helps maintain the memory of the CTLs, enabling them to respond quickly to future infections.

Objective of the Study

  • The aim of the research was to identify widely recognized epitopes of EIAV by Th1 cells. Finding such epitopes would possibly pave the way for better vaccines that can trigger strong CTL responses in infected horses, regardless of their genetic differences.

Study Methodology and Findings

  • To identify the Th1 epitopes, the researchers tested peripheral blood mononuclear cells (white blood cells) from 10 genetically different EIAV-infected horses. Specifically, the recognition of peptides from Gag p26 capsid region and a portion of Pol, which are highly conserved among different EIAV strains, were assessed.
  • They found that certain peptides – Gag 221-245, Gag 242-261 and Pol 323-344 – were recognized by a majority of the horses. Interestingly, the Gag peptides were recognized by two other horses only after their initial EIAV infection was resolved, indicating that these peptides can truly evoke an immune response early in infection.
  • The immune cells responding to the Gag peptide produced IFN-gamma, validating a Th1 response. Pol 323-344-responsive cells produced IFN-gamma both with and without the involvement of another signaling molecule, interleukin-4.
  • The researchers concluded that CD4(+) T lymphocytes are critical for these immune responses, as shown by assays using CD4- and CD8-depleted immune cells.

Implications of the Study

  • The identification of the broadly recognized EIAV Th1 epitopes offers new insights for the development of more effective vaccines against EIAV. These vaccines could possibly stimulate a robust CTL response, thereby providing better resistance to the virus among horses with varying genetic backgrounds.

Cite This Article

APA
Fraser DG, Oaks JL, Brown WC, McGuire TC. (2002). Identification of broadly recognized, T helper 1 lymphocyte epitopes in an equine lentivirus. Immunology, 105(3), 295-305. https://doi.org/10.1046/j.0019-2805.2001.01370.x

Publication

Immunology
ISSN: 0019-2805
NlmUniqueID: 0374672
Country: England
Language: English
Volume: 105
Issue: 3
Pages: 295-305

Researcher Affiliations

Fraser, Darrilyn G
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040, USA. darrilyn@vetmed.wsu.edu
Oaks, J Lindsay
    Brown, Wendy C
      McGuire, Travis C

        MeSH Terms

        • Animals
        • Antigens, Viral / analysis
        • Carrier State / immunology
        • Cell Division / immunology
        • Cells, Cultured
        • Epitopes, T-Lymphocyte / analysis
        • Equine Infectious Anemia / immunology
        • Gene Products, gag / immunology
        • Gene Products, pol / immunology
        • Horses
        • Infectious Anemia Virus, Equine / immunology
        • Interferon-gamma / biosynthesis
        • Interleukin-4 / biosynthesis
        • Leukocytes, Mononuclear / immunology
        • Peptide Fragments / immunology
        • Th1 Cells / immunology

        Grant Funding

        • F32 AI010528 / NIAID NIH HHS
        • AI07025 / NIAID NIH HHS
        • AI24291 / NIAID NIH HHS
        • T32 AI007025 / NIAID NIH HHS
        • AI10528 / NIAID NIH HHS

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        Citations

        This article has been cited 4 times.
        1. Tagmyer TL, Craigo JK, Cook SJ, Even DL, Issel CJ, Montelaro RC. Envelope determinants of equine infectious anemia virus vaccine protection and the effects of sequence variation on immune recognition.. J Virol 2008 Apr;82(8):4052-63.
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        4. Fraser DG, Mealey RH, McGuire TC. Selecting peptides to optimize Th1 responses to an equine lentivirus using HLA-DR binding motifs and defined HIV-1 Th peptides.. Immunogenetics 2003 Oct;55(7):508-14.
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