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

Robert H Mealey; Jae-Hyung Lee; Steven R Leib; Matt H Littke; Travis C McGuire

doi:10.4049/jimmunol.177.10.7377

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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

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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

Robert H Mealey, Jae-Hyung Lee, Steven R Leib, Matt H Littke and Travis C McGuire

The Journal of immunology (1950), Vol.177(10), pp.7377-7390

11/15/2006

DOI: https://doi.org/10.4049/jimmunol.177.10.7377

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https://hdl.handle.net/2376/103948

PMID: 17082657

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Abstract

Cytotoxicity Tests, Immunologic

Amino Acid Substitution - immunology

Molecular Sequence Data

Crystallography, X-Ray

Male

Infectious Anemia Virus, Equine - immunology

Gene Products, gag - chemistry

Histocompatibility Antigens Class I - metabolism

Gene Products, rev - metabolism

Computer Simulation

Gene Products, rev - chemistry

Female

Epitopes, T-Lymphocyte - immunology

Protein Structure, Tertiary

T-Lymphocytes, Cytotoxic - immunology

Amino Acid Sequence

Gene Products, gag - immunology

Histocompatibility Antigens Class I - immunology

Antigen Presentation - immunology

Histocompatibility Antigens Class I - chemistry

Protein Binding - immunology

Gene Products, rev - immunology

Gene Products, gag - metabolism

Epitopes, T-Lymphocyte - chemistry

Infectious Anemia Virus, Equine - chemistry

Animals

T-Lymphocytes, Cytotoxic - metabolism

Alleles

Horses

Epitopes, T-Lymphocyte - metabolism

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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Title: 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
Creators: Robert H Mealey - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA. rhm@vetmed.wsu.edu
Jae-Hyung Lee
Steven R Leib
Matt H Littke
Travis C McGuire
Publication Details: The Journal of immunology (1950), Vol.177(10), pp.7377-7390
Academic Unit: Veterinary Clinical Sciences, Department of
Publisher: United States
Grant note: AI058787 / NIAID NIH HHS CA97936 / NCI NIH HHS R21 AI060395 / NIAID NIH HHS AI060395 / NIAID NIH HHS R21 CA097936 / NCI NIH HHS R21 AI067125 / NIAID NIH HHS R21 AI058787 / NIAID NIH HHS AI067125 / NIAID NIH HHS
Identifiers: 99900546755301842
Language: English
Resource Type: Journal article