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Home / Equine Research Bank / J Immunol / A single amino acid difference within the alpha-2 domain of ...
Journal of immunology (Baltimore, Md. : 1950)2006; 177(10); 7377-7390; doi: 10.4049/jimmunol.177.10.7377

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.

Abstract: Although CTL are critical for control of lentiviruses, including equine infectious anemia virus, relatively little is known regarding the MHC class I molecules that present important epitopes to equine infectious anemia virus-specific CTL. The equine class I molecule 7-6 is associated with the equine leukocyte Ag (ELA)-A1 haplotype and presents the Env-RW12 and Gag-GW12 CTL epitopes. Some ELA-A1 target cells present both epitopes, whereas others are not recognized by Gag-GW12-specific CTL, suggesting that the ELA-A1 haplotype comprises functionally distinct alleles. The Rev-QW11 CTL epitope is also ELA-A1-restricted, but the molecule that presents Rev-QW11 is unknown. To determine whether functionally distinct class I molecules present ELA-A1-restricted CTL epitopes, we sequenced and expressed MHC class I genes from three ELA-A1 horses. Two horses had the 7-6 allele, which when expressed, presented Env-RW12, Gag-GW12, and Rev-QW11 to CTL. The other horse had a distinct allele, designated 141, encoding a molecule that differed from 7-6 by a single amino acid within the alpha-2 domain. This substitution did not affect recognition of Env-RW12, but resulted in more efficient recognition of Rev-QW11. Significantly, CTL recognition of Gag-GW12 was abrogated, despite Gag-GW12 binding to 141. Molecular modeling suggested that conformational changes in the 141/Gag-GW12 complex led to a loss of TCR recognition. These results confirmed that the ELA-A1 haplotype is comprised of functionally distinct alleles, and demonstrated for the first time that naturally occurring MHC class I molecules that vary by only a single amino acid can result in significantly different patterns of epitope recognition by lentivirus-specific CTL.
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Publication Date: 2006-11-04 PubMed ID: 17082657PubMed Central: PMC3342702DOI: 10.4049/jimmunol.177.10.7377Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't
  • Research Support
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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 investigates a single amino acid difference in two naturally occurring equine Major Histocompatibility Complex (MHC) class I molecules. This small variation alters how the immune system of a horse recognises certain antigens associated with equine infectious anemia virus (EIAV), a lentivirus. The study discovers that the recognition of Gag and Rev epitopes by virus-specific Cytotoxic T Lymphocytes (CTL) is significantly affected by this single amino acid difference.

Understanding Equine MHC class I molecules and EIAV

  • The study primarily focuses on understanding the MHC class I molecules, which play a pivotal role in equine immune response, particularly against the lentivirus, Equine Infectious Anemia Virus (EIAV).
  • MHC class I molecules present important epitopes (part of an antigen that is recognized by the immune system) to the virus-specific CTL, which are critical for the control of lentiviruses.
  • The research examines the role and characteristics of the equine class I molecule 7-6, which is associated with the Equine Leukocyte Antigen (ELA)-A1 haplotype and it presents the Env-RW12 and Gag-GW12 CTL epitopes. It is also noted that some ELA-A1 target cells present both epitopes while others do not recognize by Gag-GW12-specific CTL, implying the ELA-A1 haplotype comprises multiple functional alleles.

Identifying Distinct MHC Class I Molecules

  • The researchers sequenced and expressed MHC class I genes from three ELA-A1 horses to determine distinct class I molecules present in ELA-A1-restricted CTL epitopes.
  • Two horses had the 7-6 allele, and when expressed, it presented Env-RW12, Gag-GW12, and Rev-QW11 to CTL. In contrast, the third horse had a distinct allele, designated 141, which differed from 7-6 by just one amino acid in the alpha-2 domain.

Impact of the Single Amino Acid Difference

  • The single amino acid substitution did not affect the recognition of Env-RW12, but significantly improved the recognition of Rev-QW11.
  • The recognition of Gag-GW12 by CTL was completely halted, despite Gag-GW12 binding to the 141 allele. The researchers hypothesize that this lack of CTL recognition is due to molecular changes in the 141/Gag-GW12 complex, altering its shape and subsequently hampering the T-Cell Receptor’s (TCR) ability to recognize it.
  • The results of the study confirmed the existence of functionally distinct alleles within the ELA-A1 haplotype. Additionally, this was the first demonstration that a single amino acid variation in naturally occurring MHC class I molecules can lead to significant differences in epitope recognition by lentivirus-specific CTL, thus leading to different immune responses within the same species.

Cite This Article

APA
Mealey RH, Lee JH, Leib SR, Littke MH, McGuire TC. (2006). 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, 177(10), 7377-7390. https://doi.org/10.4049/jimmunol.177.10.7377

Publication

Journal of immunology (Baltimore, Md. : 1950)
ISSN: 0022-1767
NlmUniqueID: 2985117R
Country: United States
Language: English
Volume: 177
Issue: 10
Pages: 7377-7390

Researcher Affiliations

Mealey, Robert H
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA. rhm@vetmed.wsu.edu
Lee, Jae-Hyung
    Leib, Steven R
      Littke, Matt H
        McGuire, Travis C

          MeSH Terms

          • Alleles
          • Amino Acid Sequence
          • Amino Acid Substitution / immunology
          • Animals
          • Antigen Presentation / immunology
          • Computer Simulation
          • Crystallography, X-Ray
          • Cytotoxicity Tests, Immunologic
          • Epitopes, T-Lymphocyte / chemistry
          • Epitopes, T-Lymphocyte / immunology
          • Epitopes, T-Lymphocyte / metabolism
          • Female
          • Gene Products, gag / chemistry
          • Gene Products, gag / immunology
          • Gene Products, gag / metabolism
          • Gene Products, rev / chemistry
          • Gene Products, rev / immunology
          • Gene Products, rev / metabolism
          • Histocompatibility Antigens Class I / chemistry
          • Histocompatibility Antigens Class I / immunology
          • Histocompatibility Antigens Class I / metabolism
          • Horses
          • Infectious Anemia Virus, Equine / chemistry
          • Infectious Anemia Virus, Equine / immunology
          • Male
          • Molecular Sequence Data
          • Protein Binding / immunology
          • Protein Structure, Tertiary
          • T-Lymphocytes, Cytotoxic / immunology
          • T-Lymphocytes, Cytotoxic / metabolism

          Grant Funding

          • R21 AI058787 / NIAID NIH HHS
          • AI067125 / NIAID NIH HHS
          • R21 CA097936 / NCI NIH HHS
          • CA97936 / NCI NIH HHS
          • AI058787 / NIAID NIH HHS
          • R21 AI060395 / NIAID NIH HHS
          • R21 AI067125 / NIAID NIH HHS
          • AI060395 / NIAID NIH HHS

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