Presentation and binding affinity of equine infectious anemia virus CTL envelope and matrix protein epitopes by an expressed equine classical MHC class I molecule.
Abstract: Control of a naturally occurring lentivirus, equine infectious anemia virus (EIAV), occurs in most infected horses and involves MHC class I-restricted, virus-specific CTL. Two minimal 12-aa epitopes, Env-RW12 and Gag-GW12, were evaluated for presentation by target cells from horses with an equine lymphocyte Ag-A1 (ELA-A1) haplotype. Fifteen of 15 presented Env-RW12 to CTL, whereas 11 of 15 presented Gag-GW12. To determine whether these epitopes were presented by different molecules, MHC class I genes were identified in cDNA clones from Arabian horse A2152, which presented both epitopes. This horse was selected because it is heterozygous for the SCID trait and is used to breed heterozygous females. Offspring with SCID are used as recipients for CTL adoptive transfer, and normal offspring are used for CTL induction. Four classical and three putative nonclassical full-length MHC class I genes were found. Human 721.221 cells transduced with retroviral vectors expressing each gene had equine MHC class I on their surface. Following peptide pulsing, only cells expressing classical MHC class I molecule 7-6 presented Env-RW12 and Gag-GW12 to CTL. Unlabeled peptide inhibition of (125)I-labeled Env-RW12 binding to 7-6-transduced cells demonstrated that Env-RW12 affinity was 15-fold higher than Gag-GW12 affinity. Inhibition with truncated Env-RW12 demonstrated that amino acid positions 1 and 12 were necessary for binding, and single substitutions identified positions 2 and 3 as possible primary anchor residues. Since MHC class I 7-6 presented both epitopes, outbred horses with this allele can be immunized with these epitopes to optimize CTL responses and evaluate their effectiveness against lentiviral challenge.
Publication Date: 2003-08-07 PubMed ID: 12902502DOI: 10.4049/jimmunol.171.4.1984Google 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
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The article presents a study on how certain proteins identified as epitopes in equine infectious anemia virus (EIAV) interact with equine MHC class I molecules, and how this understanding can possibly contribute to developing more effective antiviral treatments.
Research Context and Aim
- The research focuses on the control of a naturally occurring lentivirus called equine infectious anemia virus (EIAV).
- MHC class I-restricted, virus-specific CTL has a significant role in controlling EIAV in infected horses.
- The study aimed to evaluate two minimal 12-aa epitopes, Env-RW12 and Gag-GW12, for their presentation by target cells from horses with an equine lymphocyte Ag-A1 (ELA-A1) haplotype.
Study Process and Findings
- Cells from Arabian horse A2152, which presented both epitopes, were used in the study as this horse was heterozygous for the SCID trait and used to breed heterozygous females.
- 7-6, which was one among the four classical and three putative nonclassical full-length MHC class I genes identified in the Arabian horse, was the only one that expressed and presented both epitopes to CTL after peptide pulsing.
- Moreover, the binding affinity of Env-RW12 to the MHC class I molecule turned out to be 15 times higher than Gag-GW12.
- Experiments with truncated Env-RW12 showed that amino acid positions 1 and 12 are essential for binding. Furthermore, positions 2 and 3 were identified as possible primary anchor residues through single substitutions.
Implications and Conclusions
- Since MHC class I 7-6 presented both epitopes, horses having this allele can be immunized with these epitopes to optimize CTL responses.
- The research provides valuable insights into the nature of EIAV interaction with the equine immune system, leading to potential avenues for developing more effective treatments against lentiviral challenges.
Cite This Article
APA
McGuire TC, Leib SR, Mealey RH, Fraser DG, Prieur DJ.
(2003).
Presentation and binding affinity of equine infectious anemia virus CTL envelope and matrix protein epitopes by an expressed equine classical MHC class I molecule.
J Immunol, 171(4), 1984-1993.
https://doi.org/10.4049/jimmunol.171.4.1984 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University College of Veterinary Medicine, Pullman, WA 99164, USA. mcguiret@vetmed.wsu.edu
MeSH Terms
- Amino Acid Substitution / genetics
- Amino Acid Substitution / immunology
- Animals
- Antigen Presentation / genetics
- B-Lymphocytes / immunology
- B-Lymphocytes / metabolism
- Cell Line, Transformed
- Cloning, Molecular
- Cytotoxicity, Immunologic / genetics
- Epitopes, T-Lymphocyte / genetics
- Epitopes, T-Lymphocyte / immunology
- Epitopes, T-Lymphocyte / metabolism
- Gene Expression Regulation / immunology
- Gene Library
- Gene Products, env / genetics
- Gene Products, env / immunology
- Gene Products, env / metabolism
- Gene Products, gag / genetics
- Gene Products, gag / immunology
- Gene Products, gag / metabolism
- Genes, MHC Class I
- Histocompatibility Antigens Class I / biosynthesis
- Histocompatibility Antigens Class I / genetics
- Histocompatibility Antigens Class I / immunology
- Histocompatibility Antigens Class I / metabolism
- Horses
- Humans
- Infectious Anemia Virus, Equine / immunology
- Male
- Peptide Fragments / genetics
- Peptide Fragments / immunology
- Peptide Fragments / metabolism
- Protein Binding / genetics
- Protein Binding / immunology
- RNA, Messenger / genetics
- T-Lymphocytes, Cytotoxic / immunology
- T-Lymphocytes, Cytotoxic / metabolism
- Viral Matrix Proteins / genetics
- Viral Matrix Proteins / immunology
- Viral Matrix Proteins / metabolism
Grant Funding
- K08 AI001575 / NIAID NIH HHS
- AI01575 / NIAID NIH HHS
- AI24291 / NIAID NIH HHS
- AI47660 / NIAID NIH HHS
Citations
This article has been cited 16 times.- Vasoya D, Tzelos T, Benedictus L, Karagianni AE, Pirie S, Marr C, Oddsdóttir C, Fintl C, Connelley T. High-Resolution Genotyping of Expressed Equine MHC Reveals a Highly Complex MHC Structure.. Genes (Basel) 2023 Jul 10;14(7).
- Bergmann T, Moore C, Sidney J, Miller D, Tallmadge R, Harman RM, Oseroff C, Wriston A, Shabanowitz J, Hunt DF, Osterrieder N, Peters B, Antczak DF, Sette A. The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires.. Immunogenetics 2015 Nov;67(11-12):675-89.
- Liu L, Wan Y, Wu L, Sun J, Li H, Li H, Ma L, Shao Y. Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine.. Retrovirology 2010 Sep 1;7:71.
- Ramsay JD, Leib SR, Orfe L, Call DR, Tallmadge RL, Fraser DG, Mealey RH. Development of a DNA microarray for detection of expressed equine classical MHC class I sequences in a defined population.. Immunogenetics 2010 Sep;62(9):633-9.
- Tallmadge RL, Campbell JA, Miller DC, Antczak DF. Analysis of MHC class I genes across horse MHC haplotypes.. Immunogenetics 2010 Mar;62(3):159-72.
- Mealey RH, Leib SR, Littke MH, Wagner B, Horohov DW, McGuire TC. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen.. Vaccine 2009 Apr 21;27(18):2453-68.
- Mealey RH, Stone DM, Hines MT, Alperin DC, Littke MH, Leib SR, Leach SE, Hines SA. Experimental Rhodococcus equi and equine infectious anemia virus DNA vaccination in adult and neonatal horses: effect of IL-12, dose, and route.. Vaccine 2007 Oct 23;25(43):7582-97.
- Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: lack of correlation between in vitro activity and in vivo efficacy.. Vet Immunol Immunopathol 2008 Jan 15;121(1-2):8-22.
- Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. Cloning and large-scale expansion of epitope-specific equine cytotoxic T lymphocytes using an anti-equine CD3 monoclonal antibody and human recombinant IL-2.. Vet Immunol Immunopathol 2007 Jul 15;118(1-2):121-8.
- 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.
- Tallmadge RL, Lear TL, Antczak DF. Genomic characterization of MHC class I genes of the horse.. Immunogenetics 2005 Nov;57(10):763-74.
- Fraser DG, Leib SR, Zhang BS, Mealey RH, Brown WC, McGuire TC. Lymphocyte proliferation responses induced to broadly reactive Th peptides did not protect against equine infectious anemia virus challenge.. Clin Diagn Lab Immunol 2005 Aug;12(8):983-93.
- Mealey RH, Sharif A, Ellis SA, Littke MH, Leib SR, McGuire TC. 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 2005 Aug 15;339(1):110-26.
- Lindesmith L, Moe C, Lependu J, Frelinger JA, Treanor J, Baric RS. Cellular and humoral immunity following Snow Mountain virus challenge.. J Virol 2005 Mar;79(5):2900-9.
- Patton KM, McGuire TC, Fraser DG, Hines SA. Rhodococcus equi-infected macrophages are recognized and killed by CD8+ T lymphocytes in a major histocompatibility complex class I-unrestricted fashion.. Infect Immun 2004 Dec;72(12):7073-83.
- Mealey RH, Leib SR, Pownder SL, McGuire TC. Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection.. J Virol 2004 Sep;78(17):9295-305.
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