FASEB J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by DIEKMAN, A. B.
Right arrow Articles by HERR, J. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by DIEKMAN, A. B.
Right arrow Articles by HERR, J. C.
(The FASEB Journal. 1999;13:1303-1313.)
© 1999 FASEB

N-linked glycan of a sperm CD52 glycoform associated with human infertility

ALAN B. DIEKMAN, ELIZABETH J. NORTON, KENNETH L. KLOTZ, V. ANNE WESTBROOK, HIROAKI SHIBAHARA1, SØREN NAABY-HANSEN2, CHARLES J. FLICKINGER and JOHN C. HERR3

Center for Recombinant Gamete Contraceptive Vaccinogens, Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA

3Correspondence: Department of Cell Biology, University of Virginia Health Sciences Center, Box 439, Charlottesville, VA 22908, USA. E-mail: jch7k{at}virginia.edu

In a benchmark study, Isojima and colleagues established H6–3C4, the first successful heterohybridoma immortalized from the peripheral blood lymphocytes of an infertile woman who exhibited high sperm-immobilizing antibody titers. The present report demonstrates the identity between the glycoprotein antigens recognized by the human H6–3C4 monoclonal antibody (mAb) and the murine S19 mAb, generated in our laboratory to sperm agglutination antigen-1 (SAGA-1). Both mAb's recognize N-linked carbohydrate epitopes on the 15–25 kDa, polymorphic SAGA-1 glycoprotein that is localized to all domains of the human sperm surface. Treatment with phosphatidylinositol-specific phospholipase C demonstrated that SAGA-1 is anchored in the sperm plasmalemma via a GPI-lipid linkage. Immunoaffinity purification and microsequencing indicated that the core peptide of the SAGA-1 glycoprotein is identical to the sequence of CD52, a GPI-anchored lymphocyte differentiation marker implicated in signal transduction. Comparison of anti-SAGA-1 and anti-CD52 immunoreactivities revealed that the sperm form of CD52 exhibits N-linked glycan epitopes, including the epitope recognized by the infertility-associated H6–3C4 mAb, which are not detected on lymphocyte CD52. Thus, the two populations of the CD52 glycoprotein on lymphocytes and spermatozoa represent glycoforms, glycoprotein isoforms with the same core amino acid sequence but different carbohydrate structures. Furthermore, mAb's to the unique carbohydrate epitopes on sperm CD52 have multiple inhibitory effects on sperm function, including a cytotoxic effect on spermatozoa in the presence of complement. These results are the first to implicate unique carbohydrate moieties of a sperm CD52 glycoform as target epitopes in the anti-sperm immune response of an infertile woman. Furthermore, localization of CD52 on all domains of the sperm surface coupled with the multiple sperm-inhibitory effects of antibodies to its unique carbohydrate moieties suggest opportunities for immunocontraceptive development.—Diekman, A. B., Norton, E. J., Klotz, K. L., Westbrook, V. A., Shibahara, H., Naaby-Hansen, S., Flickinger, C. J., Herr, J. C. N-linked glycan of a sperm CD52 glycoform associated with human infertility.


Key Words: autoimmunity • isoimmunity • glycocalyx • lymphocyte • contraception




This article has been cited by other articles:


Home page
 J AndrolHome page
M. J. Wolkowicz, L. Digilio, K. Klotz, J. Shetty, C. J. Flickinger, and J. C. Herr
Equatorial Segment Protein (ESP) Is a Human Alloantigen Involved in Sperm-Egg Binding and Fusion
J Androl, May 1, 2008; 29(3): 272 - 282.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
S. Parry, N.-K. Wong, R. L Easton, M. Panico, S. M Haslam, H. R Morris, P. Anderson, K. L Klotz, J. C Herr, A. B Diekman, et al.
The sperm agglutination antigen-1 (SAGA-1) glycoforms of CD52 are O-glycosylated
Glycobiology, October 1, 2007; 17(10): 1120 - 1126.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
A. Hasegawa, Y. Fu, H. Tsubamoto, Y. Tsuji, H. Sawai, S. Komori, and K. Koyama
Epitope analysis for human sperm-immobilizing monoclonal antibodies, MAb H6-3C4, 1G12 and campath-1
Mol. Hum. Reprod., June 1, 2003; 9(6): 337 - 343.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
T. C. McCauley, B. E. Kurth, E. J. Norton, K. L. Klotz, V. A. Westbrook, A. J. Rao, J. C. Herr, and A. B. Diekman
Analysis of a Human Sperm CD52 Glycoform in Primates: Identification of an Animal Model for Immunocontraceptive Vaccine Development
Biol Reprod, June 1, 2002; 66(6): 1681 - 1688.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
E.J. Norton, A.B. Diekman, V.A. Westbrook, C.J. Flickinger, and J.C. Herr
RASA, a recombinant single-chain variable fragment (scFv) antibody directed against the human sperm surface: implications for novel contraceptives
Hum. Reprod., September 1, 2001; 16(9): 1854 - 1860.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
C.H. Yeung, F. Perez-Sanchez, S. Schroter, C. Kirchhoff, and T.G. Cooper
Changes of the major sperm maturation-associated epididymal protein HE5 (CD52) on human ejaculated spermatozoa during incubation in capacitation conditions
Mol. Hum. Reprod., July 1, 2001; 7(7): 617 - 624.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by The Federation of American Societies for Experimental Biology.