Preliminary studies of the feline histocompatibility system

Pollack, Marilyn S.; Mastrota, Frances; Chin-Louie, Jacqueline; Mooney, S; Hayes, A. A.

doi:10.1007/bf00372305

Cited by 29 publications

(16 citation statements)

References 14 publications

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“…In most species, the rejection of grafts is almost always followed by the appearance of lymphocytotoxic alloantibodies in the host's serum (7,32,33). We also failed to detect lymphocytotoxic alloantibodies in multiparous or transfused cats, as have others (13), but most mammalian species readily develop alloantibodies after similar challenges (7,32,33 1; 9g-FLA3.2, 3.3, 3.4, 4.1, 4.2; 10i-FLA2.2; 12k-FLA2.1, 3.3; -, none (see Table 3). these species' MHC are located.…”

Section: Discussionsupporting

confidence: 44%

Section: Introductionmentioning

confidence: 99%

“…The characterization of the feline MHC as a prerequisite for the study of disease progression has been difficult because of an apparent inability to raise typing alloantisera in the cat (13). Early observations that cats show prolonged allograft survival (14)(15)(16), fail to develop lymphocytotoxic alloantibodies after pregnancy or transfusions (13), and succumb to multiple viral infections have led to speculation that cats may have limited or no polymorphism at the MHC (7,13). However, recent reports suggest that domestic cats do have polymorphic class I genes and MHC gene products (17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

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Genetic characterization of FLA, the cat major histocompatibility complex.

Winkler¹,

Schultz²,

Cevario³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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The major histocompatibility complex (MHC) of the domestic cat (termed FLA) has been refractile to genetic and serological definition largely because of repeated failure to detect cytotoxic antibodies in multiparous cats or to elicit antibody following allogeneic lymphocyte immunization. We have developed a protocol for producing cytotoxic alloantisera in the cat following rejection of multiple surgical skin grafts. Of 59 cats subjected to grafting, 13 produced lymphocytotoxic antisera which had varying specificities among a panel of outbred cat cells. A population cluster analysis of the 13 alloantisera permitted the identification of six clusters of overlapping FLA specificities. The major histocompatibility complex (MHC) is a multigene cluster in mammals encoding two distinct classes of molecules involved in the presentation of foreign antigen to the T-cell receptor (1-5). Class I genes encode a 45-kDa glycoprotein that is noncovalently linked with an invariant light chain, P2-microglobulin (f82m), on the surfaces of virtually all nucleated cells (4, 6). Class II genes encode the heavy (32-35 kDa) and light (25-28 kDa) subunits of the noncovalently associated af3 heterodimeric glycoproteins expressed on the surfaces of antigen-presenting cells and activated T cells (5). By serological analysis, both class I and class II antigens are abundantly polymorphic in most outbred species. DNA restriction analysis has also revealed extensive polymorphism of the MHC of mice, humans, and several other species (7,8). The function of both class I and class II antigens is to present foreign, often viral, antigen to the T cell receptor. In this way, the cellular immune response is directed to parasitized cells instead of free virus particles (9,10).The domestic cat is an important model for at least two viral diseases of the immune system in humans, human T cell leukemia and acquired immunodeficiency syndrome (AIDS) (11,12). The characterization of the feline MHC as a prerequisite for the study of disease progression has been difficult because of an apparent inability to raise typing alloantisera in the cat (13 MATERIALS AND METHODSDetails of allograft transplantation are described elsewhere (ref. 21; C.W. and S.O., unpublished data). Briefly, split thickness skin grafts were surgically exchanged between selected cats at 21-day intervals. In some cases, intraperitoneal booster injections of peripheral blood lymphocytes (PBLs) from 15 ml of blood were performed at 4-day intervals after grafting (21). Serum was collected from graft cats weekly and used in a cat complement-dependent cytotoxicity assay. A modification of a two-stage assay using 51Cr release as an indicator ofcell death was used to detect alloantibodies against donor cat lymphocytes. The monoclonal antibody W6/32 (23), specific for human class I heavy chain, and the monoclonal antibodies IB5 (human DR and DQ specific) (24) and ISCR3 (mouse I-EK specific) (25) were used as positive controls in immunoprecipitation experiments.Interleukin 2-stimulated or fr...

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Section: Discussionsupporting

confidence: 44%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic characterization of FLA, the cat major histocompatibility complex.

Winkler¹,

Schultz²,

Cevario³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…2, 3). Loss of the DQ and DP genes may be the reason for a remarkable immunological "tolerance" seen in cats from several perspectives, including: (1) the lack of cytotoxic antibody production (including IgE) in multiparous cats (Pollack et al 1982;Winkler et al 1989), (2) very inefficient antibody induction; only 13 of 59 domestic cats (22%) produced detectable levels of antibodies following allogenic lymphocyte immunization and skin graft transplantation (Winkler et al 1989), and (3) a remarkable tolerance for allogenic bone marrow and tissue transplants among noninbred cats used in gene therapy protocols (Simonaro et al 1999;Sun et al 1999). The critical role of class II gene families in antibody production would support the notion that DP/DQ loss in domestic cats contributes to quantitative diminution of antibody recognition and induction.…”

Section: Discussionmentioning

confidence: 99%

Comparative Genome Organization of Human, Murine, and Feline MHC Class II Region

Yuhki¹,

Beck²,

Stephens³

et al. 2003

Genome Res.

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To study comparative molecular dynamics in the genesis of the major histocompatibility complex (MHC), we determined a complete nucleotide sequence spanning 758,291 bp of the domestic cat (Felis catus) extended and classical class II region. The feline class II MHC includes 44 genes (31 predicted to be expressed) which display DNA sequence homology and ordered gene synteny with human HLA and mouse H2, in extended class II and centromere proximal regions (DM to DO) of the classical class II region. However, remarkable genomic alterations including gene gain and loss plus size differentials of 250 kb are evident in comparisons of the cat class II with those of human and mouse. The cat MHC lacks the entire DQ region and retains only relict pseudogene homologs of DP genes, compensated by expansion and reorganization of seven modern DR genes. Repetitive gene families within the feline MHC comprise 35% of the feline MHC with very different density and abundance of GC levels, SINES, LINES, STRs, and retro-elements from the same repeats in human and mouse MHC. Comparison of the feline MHC with the murine and human MHC offers a detailed view of the consequences of genome organization in three mammalian lineages.The vertebrate major histocompatibility complex (MHC) offers an unusual opportunity for comparative genomics, as it consists of a chromosomally linked community of over 100 expressed genes, nearly half having a defined role in immune defenses. A complete sequence of human HLA (3.6 Mb), chicken B-locus (92 kb), and a partial mouse H2 sequence (4.0 Mb) have been determined (Kaufman et al. 1999; The MHC Sequencing Consortium 1999;Shiina et al. 1999;Stephens et al. 1999;Yu et al. 2000;Takada et al. 2003; L. Rowen, pers. comm.). Initial comparisons reveal remarkable differences in gene inclusion, gene order, and sequence divergence, likely driven by natural selective pressures of infectious disease outbreaks in the ancestors of these species (Doherty and Zinkernagel 1976;Klein 1986;Parham and Ohta 1996;Zinkernagel 1996;Hughes and Yeager 1998;Carrington et al. 1999). A deep understanding of the immunological functions, disease influences, evolutionary constraints, and driving forces of MHC adaptation in several mammalian species provides a fertile venue to discern and interpret adaptive events which predate living vertebrate genomes.HLA, the human MHC, is composed of 224 tightly linked genes, including 128 expressed genes, 96 pseudogenes, and repetitive elements (SINES, LINES, LTRs, and STRs) that comprise nearly 50% of the sequence (The MHC Sequencing Consortium 1999; Shiina et al. 1999). The mouse MHC, H2, includes 120 expressed genes encoding functions similar to those ascribed to human MHC genes plus various pseudogenes and repeat sequences (Klein 1986;Stephens et al. 1999;Yu et al. 2000;Takada et al. 2003; L. Rowen, pers. comm.).Both human and mouse MHC show linked segments of five subregions named for the individual gene families and ordered as follows from the centromere (size of the human subregion): (1) extend...

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“…In cats, however, no matching test has been established. Serological methods and cellular immunologic procedures for MHC typing are difficult, because of inability to produce lymphocytotoxic alloantibodies following immunizations by pregnancy or transfusions [6,17,23] and weak MLR [22,24], respectively, in cats. At the present time, therefore, genotyping might be the only method for typing of MHC in cats.…”

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confidence: 99%

Genotyping of Feline MHC (FLA) Class II DRB by PCR-RFLP Method Using Group-Specific Primers.

Kuwahara

Kitoh

Kobayashi

et al. 2000

The Journal of Veterinary Medical Science

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ABSTRACT. For genotyping of feline major histocompatibility complex (FLA) class II DRB, the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method using group-specific primers was tried. Sixty-six DRB genes were classified into 8 groups according to differences in the first 5' amino acid sequences. The group-specific primers were designed as forward ones, which were specific for 5' base sequences of genes in each group. Three to 7 appropriate restricted enzymes were selected by computer analysis for RFLP typing of the genes divided into each group. In 6 out of 9 cats, the results of DRB typed by direct sequence method agreed with results of the PCR-RFLP method using group-specific primers. In the other 3 cats, the number of genes amplified by group-specific primers was 1 or 2 more than those detected by direct sequence method. The direct sequence method in 9 cats identified 5 new FLA-DRB genes. The PCR-RFLP method using group-specific primers could divide 66 genes into 37 genes and 10 subgroups from the RFLP pattern. One to 6 genes in each cat, and a total of 203 genes and subgroups were detected in 68 domestic cats. The genes detected might be biased to the subgroup G1-1a (28.8%), DRB*0501 (10.3%), G1-2a (9.4%) and G6b (7.4%). The PCR-RFLP method using group-specific primers may be useful in typing FLA class II DRB. KEY WORDS: feline, FLA class II DRB genotyping, group-specific primer, PCR-RFLP method.J. Vet. Med. Sci. 62(12): 1283-1289, 2000 Major histocompatibility complex (MHC) class II molecules are heterodimeric glycoproteins involved in the regulation of the immune responses [21]. Human leukocyte antigen (HLA) class II genes consist of various components, DR, DP, DQ and etc. [11]. However, the structure of feline MHC (FLA) class II has not been well established, and only DR genes have been detected at the present time [29]. The DRB gene which encodes the β chain of DR molecule is the most polymorphic in class II genes in humans [13], pigs [8] and dogs [3]. Polymorphism of DRB gene accumulates at the second exon, which encodes the first extracellular domain, β 1 domain of the DR β chain [10]. The type of DRB gene is associated with the result of mixed lymphocyte reaction (MLR) [1], percent of 1-year renal graft survival [22], as well as susceptibility to autoimmune diseases [21,25] in humans. Polymerase chain reaction (PCR)-sequence specific oligonucleotide probe (SSOP) method or PCR-restriction fragment length polymorphism (RFLP) method has been used commonly to distinguish the genotypes of MHC class II [9,11]. It has also been reported that digestions of PCR products by some restriction endonucleases after the PCR for grouping of alleles by group-specific primers (modified PCR-RFLP method combined with group-specific primers) were used for genotyping of human DRB1 [16].Chronic renal failure (renal sclerosis) is one of the frequent and important diseases in feline medicine. The basic therapies for this failure are fluid therapy, and administrations of antibiotics, steroids,...

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Preliminary studies of the feline histocompatibility system

Cited by 29 publications

References 14 publications

Genetic characterization of FLA, the cat major histocompatibility complex.

Genetic characterization of FLA, the cat major histocompatibility complex.

Comparative Genome Organization of Human, Murine, and Feline MHC Class II Region

Genotyping of Feline MHC (FLA) Class II DRB by PCR-RFLP Method Using Group-Specific Primers.

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