血清記憶(Serologic memory)是長期免疫效能的一個(gè)重要因素,但我們對由被HIV等重要人類病原體感染的人體中記憶B細(xì)胞所產(chǎn)生的抗體卻幾乎不了解,。為了對HIV的記憶抗體反應(yīng)進(jìn)行研究,,Scheid等人從來自具有高血清值的廣譜中和抗體的6個(gè)HIV感染者的HIV-特異性記憶B細(xì)胞中克隆出了超過500個(gè)抗體。這些患者體內(nèi)B細(xì)胞對HIV的記憶反應(yīng)由多達(dá)50個(gè)獨(dú)立的,、擴(kuò)展的B-克隆組成,這些B-克隆表達(dá)一組針對不同病毒表位(抗原決定部位)的不同抗體,,其中幾個(gè)對于廣譜HIV中和及有效免疫可能有重要作用,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 458, 636-640 (2 April 2009) | doi:10.1038/nature07930
Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
Johannes F. Scheid1,6, Hugo Mouquet1, Niklas Feldhahn1, Michael S. Seaman7, Klara Velinzon1, John Pietzsch1,8, Rene G. Ott2, Robert M. Anthony2, Henry Zebroski3, Arlene Hurley4, Adhuna Phogat9, Bimal Chakrabarti9, Yuxing Li9, Mark Connors10, Florencia Pereyra11, Bruce D. Walker11, Hedda Wardemann12, David Ho13, Richard T. Wyatt9, John R. Mascola9, Jeffrey V. Ravetch2 & Michel C. Nussenzweig1,5
1 Laboratory of Molecular Immunology,
2 Laboratory of Molecular Genetics and Immunology,
3 Proteomics Resource Center,
4 Rockefeller University Hospital, and,
5 Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA
6 Charite Universitaetsmedizin, D-10117 Berlin, Germany
7 Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
8 Institute of Chemistry and Biochemistry, Freie Universit?t Berlin, D-14195 Berlin, Germany
9 Vaccine Research Center, and,
10 Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland 20892, USA
11 Partners AIDS Research Center, Mass General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
12 Max Planck Institute for Infection Biology, D-10117 Berlin, Germany
13 Aaron Diamond Aids Research Center; New York, New York 10065, USA
Antibodies to conserved epitopes on the human immunodeficiency virus (HIV) surface protein gp140 can protect against infection in non-human primates, and some infected individuals show high titres of broadly neutralizing immunoglobulin (Ig)G antibodies in their serum. However, little is known about the specificity and activity of these antibodies1, 2, 3. To characterize the memory antibody responses to HIV, we cloned 502 antibodies from HIV envelope-binding memory B cells from six HIV-infected patients with broadly neutralizing antibodies and low to intermediate viral loads. We show that in these patients, the B-cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity neutralizing antibodies to the gp120 variable loops, the CD4-binding site, the co-receptor-binding site, and to a new neutralizing epitope that is in the same region of gp120 as the CD4-binding site. Thus, the IgG memory B-cell compartment in the selected group of patients with broad serum neutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.