Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures

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Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures. / Schoppel, K.; Haßfurther, E.; Britt, W.; Ohlin, M.; Borrebaeck, C. A K; Mach, M.

I: Virology, Vol. 216, Nr. 1, 01.02.1996, s. 133-145.

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T1 - Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures

AU - Schoppel, K.

AU - Haßfurther, E.

AU - Britt, W.

AU - Ohlin, M.

AU - Borrebaeck, C. A K

AU - Mach, M.

PY - 1996/2/1

Y1 - 1996/2/1

N2 - Glycoprotein B (gB, gpUL55) is a major antigen for the induction of neutralizing antibodies against human cytomegalovirus, making it an attractive antigen for active and passive immunoprophylaxis. The immunodominant region on gB is the antigenic domain 1 (AD-1), a complex structure which requires a minimal linear amino acid sequence of more than 75 amino acids (aa 552-635) for antibody binding. We have analyzed the fine specificity cf neutralizing and nonneutralizing AD-1-binding monoclonal antibodies. Point mutations were introduced into AD-1 and mutants were expressed as bacterial fusion proteins. The antigens were analyzed in immunoblots using a panel of 13 human and murine monoclonal antibodies. Complete loss of binding of all antibodies was observed with mutations at cysteine residues 573 and 610 as well as with a combinatorial exchange of prolines at position 577 and 613. The remaining mutations had different effects on antibody binding. Six individual recognition patterns were observed, indicating various antigenic substructures on AD-1. Changing the Fc portions of 3 murine monoclonal antibodies to human IgG1 showed that neutralization of AD-1-binding immunoglobulins is exerted by different mechanisms. Dependent on the recognized substructure within AD-1, avidity-dependent as well as Fc portion-mediated effects were observed.

AB - Glycoprotein B (gB, gpUL55) is a major antigen for the induction of neutralizing antibodies against human cytomegalovirus, making it an attractive antigen for active and passive immunoprophylaxis. The immunodominant region on gB is the antigenic domain 1 (AD-1), a complex structure which requires a minimal linear amino acid sequence of more than 75 amino acids (aa 552-635) for antibody binding. We have analyzed the fine specificity cf neutralizing and nonneutralizing AD-1-binding monoclonal antibodies. Point mutations were introduced into AD-1 and mutants were expressed as bacterial fusion proteins. The antigens were analyzed in immunoblots using a panel of 13 human and murine monoclonal antibodies. Complete loss of binding of all antibodies was observed with mutations at cysteine residues 573 and 610 as well as with a combinatorial exchange of prolines at position 577 and 613. The remaining mutations had different effects on antibody binding. Six individual recognition patterns were observed, indicating various antigenic substructures on AD-1. Changing the Fc portions of 3 murine monoclonal antibodies to human IgG1 showed that neutralization of AD-1-binding immunoglobulins is exerted by different mechanisms. Dependent on the recognized substructure within AD-1, avidity-dependent as well as Fc portion-mediated effects were observed.

UR - http://www.scopus.com/inward/record.url?scp=0342961137&partnerID=8YFLogxK

U2 - 10.1006/viro.1996.0040

DO - 10.1006/viro.1996.0040

M3 - Article

C2 - 8614980

AN - SCOPUS:0342961137

VL - 216

SP - 133

EP - 145

JO - Virology

JF - Virology

SN - 1096-0341

IS - 1

ER -