Horse cDNA clones encoding two MHC class I genes

Barbis, Dina P.; Maher, Juli K.; Stanek, Julie; Klaunberg, Brenda A.; Antczak, Douglas F.

doi:10.1007/bf00188182

Cited by 27 publications

(31 citation statements)

References 9 publications

(4 reference statements)

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“…mAb CZ3. There is no information available regarding the MHC class I genes/alleles expressed by NBL-6 and EEL cells; however, previous work has demonstrated that horse lymphocytes express the products of two polymorphic classical class I loci and may also transcribe a number of putative non-classical class I genes (Barbis et al, 1994;Ellis et al, 1995). While expression of these latter genes has not been formally demonstrated, there is evidence that one of them, C1, is expressed.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of MHC class I expression by equine herpesvirus-1

Rappocciolo

Birch

Ellis

2003

Journal of General Virology

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There is good evidence that cytotoxic T lymphocytes play an important role in the clearance of equine herpesvirus-1 (EHV1) in horses. We have demonstrated that, in common with other alphaherpesviruses, EHV1 infection can lead to dramatic down-regulation of MHC class I expression at the cell surface, a common strategy for pathogen evasion of the host immune response. This down-regulation is specific for MHC class I and does not reflect a general shut-off of host-cell protein synthesis. The use of monoclonal antibodies that recognize different MHC class I epitopes has demonstrated that the effect may be allele-or locus-specific. Use of the viral DNA synthesis inhibitor phosphonoacetic acid, which prevents late viral gene expression, showed that the effect is mediated by an immediate-early or early viral gene, and use of the protein translation inhibitor cycloheximide confirmed that an early gene is primarily responsible. The data indicate that EHV1 infection results in enhanced endocytosis of MHC class I from the cell surface; the only other herpesvirus reported to use this mechanism is human herpesvirus-8. Elucidation of the precise mechanisms used by EHV1 in this process and identification of the genes responsible may lead to improved vaccination strategies.

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Section: Discussionmentioning

confidence: 99%

Down-regulation of MHC class I expression by equine herpesvirus-1

Rappocciolo

Birch

Ellis

2003

Journal of General Virology

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“…E. coli electrocompetent cells (Invitrogen Life Technologies) were transformed with this ligation mixture resulting in a cDNA library. Clones were selected from the library by colony-lift hybridization with a 32 P-labeled HindIII-XbaI fragment from horse MHC I gene 8/9 (provided by Dr. D. Antczak, Cornell University, Ithaca, NY) (46). Positive colonies were isolated, and those with inserts of the correct size were sequenced.…”

Section: Identification Of Equine Mhc I Allelesmentioning

confidence: 99%

“…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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“…Clones with MHC class I genes were identified by hybridization with a probe made from a previously cloned equine MHC class I gene (20). One hundred and ten clones were evaluated by sequencing, and seven full-length MHC class I ␣ genes and two pseudogenes were identified.…”

Section: Classical and Putative Nonclassical Mhc Class I Genes Were Cmentioning

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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Horse cDNA clones encoding two MHC class I genes

Cited by 27 publications

References 9 publications

Down-regulation of MHC class I expression by equine herpesvirus-1

Down-regulation of MHC class I expression by equine herpesvirus-1

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

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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