Presentation and binding affinity of equine infectious anemia virus CTL envelope and matrix protein epitopes by an expressed equine classical MHC class I molecule

Travis C McGuire; Steven R Leib; Robert H Mealey; Darrilyn G Fraser; David J Prieur

doi:10.4049/jimmunol.171.4.1984

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Presentation and binding affinity of equine infectious anemia virus CTL envelope and matrix protein epitopes by an expressed equine classical MHC class I molecule

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Presentation and binding affinity of equine infectious anemia virus CTL envelope and matrix protein epitopes by an expressed equine classical MHC class I molecule

Travis C McGuire, Steven R Leib, Robert H Mealey, Darrilyn G Fraser and David J Prieur

The Journal of immunology (1950), Vol.171(4), pp.1984-1993

08/15/2003

DOI: https://doi.org/10.4049/jimmunol.171.4.1984

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https://hdl.handle.net/2376/113821

PMID: 12902502

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Abstract

Gene Products, env - immunology

Protein Binding - genetics

Viral Matrix Proteins - genetics

Humans

Amino Acid Substitution - immunology

Epitopes, T-Lymphocyte - genetics

Male

Infectious Anemia Virus, Equine - immunology

Gene Products, env - metabolism

Histocompatibility Antigens Class I - metabolism

Peptide Fragments - immunology

Cloning, Molecular

Gene Products, env - genetics

Viral Matrix Proteins - metabolism

Histocompatibility Antigens Class I - biosynthesis

Epitopes, T-Lymphocyte - immunology

Peptide Fragments - genetics

B-Lymphocytes - metabolism

T-Lymphocytes, Cytotoxic - immunology

Cytotoxicity, Immunologic - genetics

Gene Products, gag - immunology

Peptide Fragments - metabolism

Gene Products, gag - genetics

Gene Library

Gene Expression Regulation - immunology

RNA, Messenger - genetics

Histocompatibility Antigens Class I - immunology

Antigen Presentation - genetics

Histocompatibility Antigens Class I - genetics

Protein Binding - immunology

Gene Products, gag - metabolism

Animals

B-Lymphocytes - immunology

T-Lymphocytes, Cytotoxic - metabolism

Horses

Amino Acid Substitution - genetics

Genes, MHC Class I

Viral Matrix Proteins - immunology

Cell Line, Transformed

Epitopes, T-Lymphocyte - metabolism

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.

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Title: Presentation and binding affinity of equine infectious anemia virus CTL envelope and matrix protein epitopes by an expressed equine classical MHC class I molecule
Creators: Travis C McGuire - Department of Veterinary Microbiology and Pathology, Washington State University College of Veterinary Medicine, Pullman, WA 99164, USA. mcguiret@vetmed.wsu.edu
Steven R Leib
Robert H Mealey
Darrilyn G Fraser
David J Prieur
Publication Details: The Journal of immunology (1950), Vol.171(4), pp.1984-1993
Academic Unit: Veterinary Clinical Sciences, Department of
Publisher: United States
Grant note: AI01575 / NIAID NIH HHS AI47660 / NIAID NIH HHS K08 AI001575 / NIAID NIH HHS AI24291 / NIAID NIH HHS
Identifiers: 99900548212901842
Language: English
Resource Type: Journal article