alpha2,6-Sialylation promotes binding of placental protein 14 via its Ca2+-dependent lectin activity: insights into differential effects on CD45RO and CD45RA T cells.
Placental protein 14 (PP14; glycodelin) is a pregnancy-associated immunoregulatory protein that is known to inhibit T cells via T-cell receptor desensitization. The recent demonstration of PP14 as lectin has provided insight into how it may mediate its CD45 glycoprotein-dependent T-cell inhibition. In this study, we have investigated PP14's lectin-binding properties in detail. Significantly, PP14 reacts with N-acetyllactosamine (LacNAc) as was also found for members of the galectin family, such as the potent immunoregulatory protein, galectin-1. However, in contrast to galectin-1, PP14's binding is significantly enhanced by alpha2,6-sialylation and also by the presence of cations. This was demonstrated by preferential binding to fetuin as compared with its desialylated variant asialofetuin (ASF) and by using free alpha2,6- versus alpha2,3-sialylated forms of LacNAc in competitive inhibition and direct solid-phase binding assays. Interestingly, from immunological point of view, PP14 also binds differentially to CD45 isoforms known to differ in their degree of sialylation. PP14 preferentially inhibits CD45RA+, as compared with CD45RO+ T cells, and preferentially co-capped this variant CD45 on the T-cell surface. Finally, we demonstrate that PP14 promotes CD45 dimerization and clustering, a phenomenon that may regulate CD45 activity.
Ish-Shalom
Eliran
E
Goldyne Savad Institute of Gene Therayp, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Gargir
Ari
A
André
Sabine
S
Borovsky
Zipora
Z
Ochanuna
Zohar
Z
Gabius
Hans-Joachim
HJ
Tykocinski
Mark L
ML
Rachmilewitz
Jacob
J
D000017:ABO Blood-Group System / Q000276:immunology*; D002118:Calcium / Q000737:chemistry / Q000494:pharmacology*; D002413:Cations, Divalent / Q000737:chemistry; D002478:Cells, Cultured; D019281:Dimerization; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism
D000017:ABO Blood-Group System; D002413:Cations, Divalent; D000071816:Glycodelin; D006023:Glycoproteins; D037102:Lectins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D017493:Leukocyte Common Antigens; D019158:N-Acetylneuraminic Acid; D002118:Calcium