A novel class of mammalian Fc receptor binding cattle IgG2

Veterinary

Veterinary

ELSEVIER

Immunology and Immunopathology 54 (1996) 23-24

immunology and immunopathology

A novel class of mammalian Fc receptor binding cattle IgG2 C.J. Howard, G. Zhang, C.A. Tregaskes, P. Sopp, R.A. Collins, J.R. Young Institute jbr Animal He&h,

Compton, Newbury. Berkshire, RG20 7NN, UK

Three classes of FcyR that are expressed on the surface of lymphoid and myeloid cells have been identified in humans. These are FcyRI (CD64), FcyRII (CD32), FcyRIII (CD 16). A number of FcyR genes have been identified, not all of which encode molecules expressed on the cell surface; FcyRI is derived from one gene, FcyRII from three and FcyRIII from two (Ravetch and Kinet, 1991). The variable expression and function of these FcR on different cells and their differing affinities for Ig classes or subclasses results in a variety of effector responses. Comparisons with mice indicate that FcR divergence occurred before speciation. There is now unequivocal evidence demonstrating the presence of four FcyR genes in cattle but important differences are evident between cattle and humans. Three of these cattle FcyR genes are homologues of human FcyRI, FcyRII and FcyRIII. One is the first member of a novel class of mammalian FcyR. Cattle FcyRI was identified and partially sequenced from a genomic library by Symons and Clarkson (1992), but has not been expressed and no monoclonal antibodies (mab) are available. A cDNA encoding an FcR that bound complexed bovine IgGl, but not IgG2, has been sequenced and expressed (Zhang et al., 1994). This was the cattle homologue of human FcyRIIb2 indicating the presence in cattle of the FcyRIIb2 gene. Mab to this FcR (CD 32) have been produced and expression on monocytes, B cells and afferent lymph veiled cells (dendritic cells) established. A transcript in y6 TCR+T-cells in cattle was identified by RTPCR. When sequenced it appeared to be the cattle homologue of the human FcyRIIIA gene indicating likely expression of CD16 in the yS TCR+ T-cells. A cDNA encoding an FcR that bound complexed bovine IgG2, which represents a novel class of FcyR, has also been identified (Zhang et al., 1995). The cDNA was cloned by screening a cattle alveolar macrophage library made in the vector pCDM8 and expressed in COS-7 cells and expression detected with erythrocytes specifically sensitised with bovine IgG2. A search of the PIR database indicated a greater level of 0165.2427/96/$15.00 Copyright PII SO165-2427(96)05642-5

0 1996 Elsevier Science B.V. All rights reserved.

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similarity with human FccuR than with any other FcR. The percentage of identical nucleotides was 41% and amino acids 56%. This high similarity was between the extracellular and transmembrane regions, the cytoplasmic region is unrelated. Similarities (amino acids) with human FcyRI, FcyRII. FcyRIII, FcyRI or bovine FceRII were less than 28%. COS-7 cells transfected with the cloned plasmid bound erythrocytes specifically sensitised with bovine IgG2 but not IgGl. Aggregated bovine IgG2 also bound. Aggregated bovine IgGl. bovine IgA from tracheobronchial secretions and human serum IgA did not bind. This new receptor, which we have named bovine Fcy2R, represents a novel class of mammalian FcyR the evolution of which is likely to have been influenced by the truncated hinge of the bovine IgG2 molecule. Mab specific for the Fcy2R showed expression on granulocytes and monocytes. Analysis of genetic divergence of the genes encoding bovine and human FcyR and FccuR indicated that the novel cattle Fcy2R gene and the human FccuR gene probably evolved from a common ancestor which is not shared by the other FcyR.

References Ravetch and Symons and zhang et al., Zhang et al.,

Kinet. 1991, Annu. Rev. Immunol., 9: 457. Clarkson, 1992. Mol. Immunol., 29: 1407. 1994. Immunogenetics, 39: 423. 1995. J. Immunol. 155: 1534.