Abstract
CD46, until recently known as HuLy-m5, is a non-lineage restricted surface antigen ubiquitously expressed by almost all human cells except erythrocytes. The CD46 antigen is identified by the E4.3 monoclonal antibody (mAb) and exists at the surface of human peripheral blood lymphocytes (PBLs) as two acidic, non-disulfide bonded chains, α and β, ofM r 66 000 and 56 000. Receptor density analysis showed that CD46 was of moderately low abundance on PBLs with 7.5×103 molecules present on each cell. The two chains of CD46 were purified (144 000-fold) by immunoaffinity-chromatography with E4.3 mAb from the plasma membranes of a human spleen infiltrated with chronic myelogenous leukemia cells. Amino acid sequence analysis of the NH2-terminal of both α and β chains yielded the same sequence; XEEPPQ/TFEAMELIGKPKPYYEIGE. Peptide mapping studies confirmed that both CD46 chains were closely related, except for one peptide fragment. This amino acid sequence is identical to that of the NH2-terminal of the recently cloned membrane co-factor protein (MCP), a membrane protein that binds the C3b and C4b fragments of complement and acts as a co-factor for I protein-mediated decay of the complement convertases. CD46 shares a cross-reactive epitope with some primate retroviruses, and this may indicate that some retroviruses mimic the mechanisms used by autologous human cells to evade complement-mediated immune clearance.
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Ballard, L., Seya, T., Teckman, J., Lublin, D. M., and Atkinson, J. P.: A polymorphism of the complement regulatory protein MCP (membrane cofactor protein or gp45–70).J Immunol 138: 3850–3855, 1987
Carroll, M. C., Alicot, E. M., Katzman, P. J., Klickstein, L. B., Smith, J. A., and Fearon, D. T.: Organization of the genes encoding complement receptors type 1 and 2, decay-accelerating factor, and C4-binding protein in the RCA locus on human chromosome 1.J Exp Med 167: 1271–1280, 1988
Cleveland, D. W., Fischer, S. G., Kirschner, M. W., and Laemmli, U. K.: Peptide mapping by limited proteolysis in sodium dodecysulfate and analysis by gel electrophoresis.J Biol Chem 252: 1102–1106, 1977
Cohen, M. and Larson, E.: Human endogenous retroviruses.Bioessays 9: 191–213, 1988
Hewick, R. M., Hunkapiller, M. W., Hood, L. E., and Dreyer, J. W.: A gas-liquid solid phase peptide and protein sequenator.J Biol Chem 256: 7990–7997, 1981
Johnson, G. D., Holborow, E. J., and Darling, J.: Immunoflourescence and immunoenzyme techniques.In D. M. Weir (ed.):Handbook of Experimental Immunology, Third Ed, pp. 15.1–15.30, Blackwell Scientific Publications, Oxford, 1978
Lublin, D. M., Liszewsi, M. K., Post, T. W., Arce, M. A., Le Beau, M. M., Rebentisch, M. B., Lemons, R. S., Seya, T., and Atkinson, J. P.: Molecular cloning and chromosomal localization of human membrane cofactor protein (MCP): evidence for inclusion in the multigene family of complement-regulatory proteins.J Exp Med 168: 181–194, 1988
March, S. C., Parikh, I., and Cuatrecasas, P.: A simplified method for cyanogen bromide activation of agarose for affinity chromatography.Anal Biochem 60: 149–152, 1974
Mason, D. W. and Williams, A. F.: Kinetics of antibody reactions and the analysis of cell surface antigens.In D. M. Weir and L. A. Herzenberg (eds.):Handbook of Experimental Immunology, Fourth Ed, Vol 1, pp. 38.1–38.17, Blackwell Scientific Publications, Oxford, 1986
Purcell, D. F. J., Clark, G. J., Brown, M. A., McKenzie, I. F. C., Sandrin, M. S., and Deacon, N. J.: HuLy-m5, an antigen sharing epitopes with envelope gp70 molecules of primate retroviruses.In W. Knapp, W. R. Gilks, P. Reiber, R. Schmidt, H. Stein, A. von dem Boune (eds.):Leucocyte Typing IV, Oxford University Press, Oxford, in press, 1989a
Purcell, D. F. J., Deacon, N. J., and McKenzie, I. F. C.: The human non-lineage antigen CD46 (HuLy-m5) and primate retroviral gp70 molecules share protein defined antigenic determinants.Immunol and Cell Biol 67: 279–289, 1989b
Roe, R., Robbins, R. A., Loxton, R. R., and Baldwin, R. W.: Kinetics of divalent monoclonal antibody binding to tumour cell surface antigens using flow cytometry: standardisation and mathematical analysis.Mol Immunol 22: 11–21, 1985
Scatchard, D.: The attractions of proteins for small molecules and ions.Ann NY Acad Sci 51: 660–672, 1949
Seya, T., Turner, J. R., and Atkinson, J. P.: Purification and characterization of a membrane protein (gp 45–70) that is a cofactor for cleavage of C3b and C4b.J Exp Med 163: 837–855, 1986
Sparrow, R. L. and McKenzie, I. F. C.: A unique antigen physically associated with HLA molecules.Hum Immunol 7: 1–15, 1983
Sparrow, R. L., Purcell, D. F. J., and McKenzie, I. F. C.: Cross-reactivity of a normal human cell surface antigen with primate retrovirus glycoproteins.Hum Immunol 13: 83–93, 1985
Walker, I. D., Murray, B. J., Kirszbaum, L., Chambers, G. W., Deacon, N. J., and McKenzie, I. F. C.: The amino-terminal sequences of Ly-2 and Ly-3.Immunogenetics 23: 60–63, 1986
Williams, A. F. and Barclay, A. N.: Glycoprotein antigens of the lymphocyte surface and their purification by antibody affinity chromatography.In D. M. Weir and L. A. Herzenberg (eds.),Handbook of Experimental Immunology, Fourth Ed, Vol 1, pp. 22.1–22.24, Blackwell Scientific Publications, Oxford, 1986
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Purcell, D.F.J., Deacon, N.J., Andrew, S.M. et al. Human non-lineage antigen, CD46 (HuLy-m5): purification and partial sequencing demonstrates structural homology with complement-regulating glycoproteins. Immunogenetics 31, 21–28 (1990). https://doi.org/10.1007/BF00702485
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DOI: https://doi.org/10.1007/BF00702485