Marked differences in the structures and protein associations of lymphocyte and monocyte CD4: resolution of a novel CD4 isoform

Immunology and Cell Biology
G W LynchW Bret Church

Abstract

The structures, molecular interactions and functions of CD4 in a subset of T lymphocytes have been well characterized. The CD4 receptors of other cell types have, however, been poorly documented. We have previously shown that lymphocytes and monocytes/macrophages differ in their expression of CD4 monomers and dimers. In the present study, we have shown further significant differences. Variability in the blocking of CD4 mAb binding by sulfated polyanions indicated differences in exofacial CD4 structures. In contrast to the well-documented 55 kDa monomers in lymphocytic cells, monocytic cells were found to coexpress two monomer isoforms: the 55 kDa form and a novel 59 kDa species. Experimental uncoupling of CD4 disulfides indicated that the oxidized 55 kDa monomer could be converted to the 59 kDa form. This was achieved by chemical reduction of purified native or recombinant CD4, or in cell transfection experiments by mutation of cysteine to alanine in domain 1 (D1) (Cys16 or Cys84) and in domain 4 (D4) (Cys303 or Cys345). All of these modifications promote CD4 distension on SDS-PAGE analysis and indicate that, when CD4 inter-beta-sheet disulfides in the D1 and D4 Ig folds are disrupted, there is an unravelling of the oxidized fo...Continue Reading

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Citations

May 15, 2009·Journal of Virology·Nadine LaguetteStéphane Basmaciogullari
Apr 13, 2010·Retrovirology·Georges HerbeinWasim Abbas
May 3, 2011·PloS One·Rui André Saraiva RaposoWilliam James
May 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Dennis E DischerColin P Johnson
Feb 28, 2009·Journal of Neuroimmunology·Beatriz AlmoldaBernardo Castellano
Aug 16, 2014·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Dennis Van HoofEmily Park
Jun 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rui André Saraiva RaposoWilliam James
Jul 12, 2018·Canadian Journal of Gastroenterology & Hepatology·Takuya KomuraYoshio Sakai
Apr 30, 2021·Frontiers in Immunology·Sarah E JacksonMark R Wills
Oct 10, 2014·ACS Nano·Raul Perez-JimenezJulio M Fernandez

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