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Virology2005; 339(1); 110-126; doi: 10.1016/j.virol.2005.05.025

Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes.

Abstract: Cytotoxic T lymphocytes (CTL) are critical for control of lentiviruses, including equine infectious anemia virus (EIAV). Measurement of equine CTL responses has relied on chromium-release assays, which do not allow accurate quantitation. Recently, the equine MHC class I molecule 7-6, associated with the ELA-A1 haplotype, was shown to present both the Gag-GW12 and Env-RW12 EIAV CTL epitopes. In this study, 7-6/Gag-GW12 and 7-6/Env-RW12 MHC class I/peptide tetrameric complexes were constructed and used to analyze Gag-GW12- and Env-RW12-specific CTL responses in two EIAV-infected horses (A2164 and A2171). Gag-GW12 and Env-RW12 tetramer-positive CD8+ cells were identified in nonstimulated peripheral blood mononuclear cells as early as 14 days post-EIAV inoculation, and frequencies of tetramer-positive cells ranged from 0.4% to 6.7% of nonstimulated peripheral blood CD8+ cells during the 127-day study period. Although both horses terminated the initial viremic peak, only horse A2171 effectively controlled viral load. Neutralizing antibody was present during the initial control of viral load in both horses, but the ability to maintain control correlated with Gag-GW12-specific CD8+ cells in A2171. Despite Env-RW12 dominance, Env-RW12 escape viral variants were identified in both horses and there was no correlation between Env-RW12-specific CD8+ cells and control of viral load. Although Gag-GW12 CTL escape did not occur, a Gag-GW12 epitope variant arose in A2164 that was recognized less efficiently than the original epitope. These data indicate that tetramers are useful for identification and quantitation of CTL responses in horses, and suggest that the observed control of EIAV replication and clinical disease was associated with sustained CTL recognition of Gag-specific epitopes.
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Publication Date: 2005-06-28 PubMed ID: 15979679PubMed Central: PMC3342685DOI: 10.1016/j.virol.2005.05.025Google Scholar: Lookup
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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.

This research article explores how the use of major histocompatibility complex class I/peptide tetrameric complexes allow for early detection of cytotoxic T lymphocytes in horses infected with equine infectious anemia virus (EIAV), a type of lentivirus. The study specifically tracks how horses react to two primary EIAV CTL epitopes, Gag-GW12 and Env-RW12. The findings indicate that control of EIAV replication and clinical disease was associated with sustained detection of Gag-specific epitopes.

Understanding Equine Infectious Anemia Virus (EIAV)

  • The EIAV is a lentivirus, similar to the Human Immunodeficiency Virus (HIV) which causes AIDS in humans.
  • Like other lentiviruses, it primarily attacks the immune system, leading to progressive and often, fatal diseases.
  • The EIAV targets the Cytotoxic T Lymphocytes (CTLs) which play a crucial role in controlling the virus.

The Role of Major Histocompatibility Complex (MHC) Class I/Peptide Tetrameric Complexes

  • The MHC is a set of proteins that are vital for the immune system to recognize and kill infected cells.
  • The study used MHC class I molecule 7-6, associated with a specific genetic haplotype, and found it presents both Gag-GW12 and Env-RW12 EIAV CTL epitopes – pieces of the virus that immune cells can identify and target.

Significance of the Gag-GW12 and Env-RW12 Epitopes

  • The Gag-GW12 and Env-RW12 epitopes are specific protein formations on the EIAV that allow the immune system to identify and attack these cells.
  • The horses’ reaction to these epitopes, and their subsequent impact on the control of EIAV, were examined through the study.

Observations from the Study

  • The study observed that horses had detectable levels of specific CTLs associated with these two epitopes as early as 14 days post EIAV inoculation.
  • The prevalence of these cells demonstrated a fluctuating trend over a period of 127 days.
  • While a neutralizing antibody was initially present in the horses, sustained control of the viral load was only linked with the Gag-GW12-specific CTLs in horse A2171.
  • The Env-RW12 epitope, despite its dominance, didn’t show a correlation with the control of the viral load.

Conclusions from the Study

  • This study indicates that tetramers (MHC class I/peptide tetrameric complexes) can be an effective tool in identifying and quantifying CTL responses in horses infected with EIAV.
  • The findings suggest a directly proportional relationship between the control of EIAV replication and clinical disease with the continued detection of Gag-specific epitopes, alluding to the potential to use such detection methods for disease control.

Cite This Article

APA
Mealey RH, Sharif A, Ellis SA, Littke MH, Leib SR, McGuire TC. (2005). Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes. Virology, 339(1), 110-126. https://doi.org/10.1016/j.virol.2005.05.025

Publication

Virology
ISSN: 0042-6822
NlmUniqueID: 0110674
Country: United States
Language: English
Volume: 339
Issue: 1
Pages: 110-126

Researcher Affiliations

Mealey, Robert H
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. rhm@vetmed.wsu.edu
Sharif, Amin
    Ellis, Shirley A
      Littke, Matt H
        Leib, Steven R
          McGuire, Travis C

            MeSH Terms

            • Amino Acid Sequence
            • Animals
            • Epitopes / immunology
            • Equine Infectious Anemia / immunology
            • Equine Infectious Anemia / virology
            • Gene Products, env / genetics
            • Gene Products, env / immunology
            • Gene Products, gag / genetics
            • Gene Products, gag / immunology
            • Histocompatibility Antigens Class I / immunology
            • Horses
            • Infectious Anemia Virus, Equine / genetics
            • Lymphocyte Count
            • Molecular Sequence Data
            • Sequence Alignment
            • Species Specificity
            • Spiruroidea / immunology
            • T-Lymphocyte Subsets / immunology
            • T-Lymphocytes, Cytotoxic / immunology
            • Viremia

            Grant Funding

            • R21 AI058787 / NIAID NIH HHS
            • AI058787 / NIAID NIH HHS
            • AI24291 / NIAID NIH HHS

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            Citations

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