At Least Four MHC Class I Genes Are Transcribed in the Horse: Phylogenetic Analysis Suggests an Unusual Evolutionary History for the MHC in This Species

Ellis, Shirley A.; Martin, Andreas; Holmes, Edward C.; Morrison, W. Ivan

doi:10.1111/j.1744-313x.1995.tb00239.x

Cited by 45 publications

(59 citation statements)

References 24 publications

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“…Additionally, classical MHC-I genes are expressed on nearly all nucleated cells, whereas the nonclassical MHC genes are expressed on a more narrow range of cell types (25). Ellis et al identified four classical MHC-I genes (ECMHCB1-4) and three nonclassical MHC-I genes (ECMHCA1, ECMHCC1, and ECMHCE1) in the horse by sequence analyses (12). The consensus sequences of the four classical MHC-I genes are grouped together as MHCX1 (accession number NM_001099766).…”

Section: Discussionmentioning

confidence: 99%

Equus caballus Major Histocompatibility Complex Class I Is an Entry Receptor for Equine Herpesvirus Type 1

Kurtz

Singletary

Kelly

et al. 2010

J Virol

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In this study, Equus caballus major histocompatibility complex class I (MHC-I) was identified as a cellular entry receptor for the alphaherpesvirus equine herpesvirus type 1 (EHV-1). This novel EHV-1 receptor was discovered using a cDNA library from equine macrophages. cDNAs from this EHV-1-susceptible cell type were inserted into EHV-1-resistant B78H1 murine melanoma cells, these cells were infected with an EHV-1 lacZ reporter virus, and cells that supported virus infection were identified by X-Gal (5-bromo-4-chloro-3-indolyl-␤-D-galactopyranoside) staining. Positive cells were subjected to several rounds of purification to obtain homogeneous cell populations that were shown to be uniformly infected with EHV-1. cDNAs from these cell populations were amplified by PCR and then sequenced. The sequence data revealed that the EHV-1-susceptible cells had acquired an E. caballus MHC-I cDNA. Cell surface expression of this receptor was verified by confocal immunofluorescence microscopy. The MHC-I cDNA was cloned into a mammalian expression vector, and stable B78H1 cell lines were generated that express this receptor. These cell lines were susceptible to EHV-1 infection while the parental B78H1 cells remained resistant to infection. In addition, EHV-1 infection of the B78H1 MHC-I-expressing cell lines was inhibited in a dose-dependent manner by an anti-MHC-I antibody.

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Section: Discussionmentioning

confidence: 99%

Equus caballus Major Histocompatibility Complex Class I Is an Entry Receptor for Equine Herpesvirus Type 1

Kurtz

Singletary

Kelly

et al. 2010

J Virol

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“…This was demonstrated by sequencing cDNA clones containing MHC class I genes and identifying four classical and three putative nonclassical sequences. This classification was based on published sequences and criteria, including the presence of a 35-aa transmembrane domain of equine classical MHC class I molecules, in contrast to some of the putative nonclassical MHC class I molecules that have a 9-to 15-base insertion and/or a 6-base deletion in the coding sequence of the transmembrane domain (21,22). Two of the cloned nonclassical genes were exactly the same as two putative nonclassical MHC class I genes designated ncA1 and C1, while gene 7-51 was similar to a third putative nonclassical gene B3 (22).…”

Section: Discussionmentioning

confidence: 99%

Presentation and Binding Affinity of Equine Infectious Anemia Virus CTL Envelope and Matrix Protein Epitopes by an Expressed Equine Classical MHC Class I Molecule

McGuire

Leib

Mealey

et al. 2003

The Journal of Immunology

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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 125I-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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“…b, Equine MHC I molecules 7-6 and 141 differed in only one amino acid in the ␣-2 domain. Amino acid sequences of 7-6 and 141 are shown with domains (46,49) indicated. The E3 V substitution at position 152 is shown in bold.…”

Section: Target Cells From A2140 and A2152 Pulsed With Env-rw12 Gag-mentioning

confidence: 99%

A Single Amino Acid Difference within the α-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

Mealey

Lee

Leib

et al. 2006

The Journal of Immunology

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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 α-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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At Least Four MHC Class I Genes Are Transcribed in the Horse: Phylogenetic Analysis Suggests an Unusual Evolutionary History for the MHC in This Species

Cited by 45 publications

References 24 publications

Equus caballus Major Histocompatibility Complex Class I Is an Entry Receptor for Equine Herpesvirus Type 1

Equus caballus Major Histocompatibility Complex Class I Is an Entry Receptor for Equine Herpesvirus Type 1

Presentation and Binding Affinity of Equine Infectious Anemia Virus CTL Envelope and Matrix Protein Epitopes by an Expressed Equine Classical MHC Class I Molecule

A Single Amino Acid Difference within the α-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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