ABO blood group glycans modulate sialic acid recognition on erythrocytes.
ABH(O) blood group polymorphisms are based on well-known intraspecies variations in structures of neutral blood cell surface glycans in humans and other primates. Whereas natural antibodies against these glycans can act as barriers to blood transfusion and transplantation, the normal functions of this long-standing evolutionary polymorphism remain largely unknown. Although microbial interactions have been suggested as a selective force, direct binding of lethal pathogens to ABH antigens has not been reported. We show in this study that ABH antigens found on human erythrocytes modulate the specific interactions of 3 sialic acid-recognizing proteins (human Siglec-2, 1918SC influenza hemagglutinin, and Sambucus nigra agglutinin) with sialylated glycans on the same cell surface. Using specific glycosidases that convert A and B glycans to the underlying H(O) structure, we show ABH antigens stabilize sialylated glycan clusters on erythrocyte membranes uniquely for each blood type, generating differential interactions of the 3 sialic acid-binding proteins with erythrocytes from each blood type. We further show that by stabilizing such structures ABH antigens can also modulate sialic acid-mediated interaction of pathogens such as Plasmodium falciparum malarial parasite. Thus, ABH antigens can noncovalently alter the presentation of other cell surface glycans to cognate-binding proteins, without themselves being a direct ligand.
Cohen
Miriam
M
Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Hurtado-Ziola
Nancy
N
Varki
Ajit
A
D000017:ABO Blood-Group System / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001789:Blood Group Antigens / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000378:metabolism*; D005434:Flow Cytometry; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism / Q000469:parasitology; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D037121:Plant Lectins / Q000378:metabolism; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D054788:Ribosome Inactivating Proteins / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism
D000017:ABO Blood-Group System; D001789:Blood Group Antigens; D006388:Hemagglutinins; D037121:Plant Lectins; D011134:Polysaccharides; C050600:Sambucus nigra lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D054788:Ribosome Inactivating Proteins; D019158:N-Acetylneuraminic Acid
Cell. 2005 Jul 29;122(2):183-93
16051144
Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12819-24
16126901
J Biol Chem. 1989 Dec 5;264(34):20159-62
2584211
J Biol Chem. 1991 Sep 15;266(26):17552-8
1894638
J Biol Chem. 2000 Mar 24;275(12):8633-40
10722703
J Virol. 2005 Jun;79(11):6714-22
15890909
J Neurol Neurosurg Psychiatry. 2008 Oct;79(10):1148-52
18339728
Biochem J. 2000 Aug 15;350 Pt 1:53-60
10926825
Methods Mol Biol. 2007;398:245-61
18214385
Nat Biotechnol. 2007 Apr;25(4):454-64
17401360
Arch Biochem Biophys. 2004 Sep 15;429(2):145-53
15313217
FEBS Lett. 2003 Jan 16;534(1-3):185-9
12527384
Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18987-91
17142315
Methods Enzymol. 2000;312:447-58
11070893
Blood. 1990 Aug 15;76(4):842-8
2383660
Hum Genet. 2008 Sep;124(2):123-35
18629539
J Biol Chem. 2003 Nov 28;278(48):48245-50
14500706
Biochim Biophys Acta. 2001 Feb 16;1525(1-2):58-69
11342254
Tissue Antigens. 2006 Dec;68(6):459-66
17176435
Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17471-6
17959777
Science. 2004 Jul 23;305(5683):519-22
15273394
Histochem Cell Biol. 2006 May;125(5):451-6
16284775
Blood. 2007 Oct 1;110(7):2250-8
17502454
Am J Hematol. 1980;9(4):381-9
7211833
Glycoconj J. 1997 Feb;14(2):159-73
9111133
Mol Biol Evol. 1997 Apr;14(4):399-411
9100370
Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7390-7
7519775
J Biol Chem. 1999 Aug 6;274(32):22729-38
10428856
Cell. 2006 Feb 24;124(4):755-66
16497586
Biophys J. 1995 May;68(5):1881-7
7612830
Glycobiology. 2009 Jul;19(7):789-96
19349623
J Biol Chem. 1993 Apr 5;268(10):7019-27
8463235
J Clin Invest. 1994 Jan;93(1):121-30
8282779
J Mol Biol. 2006 Feb 3;355(5):1143-55
16343533
Trends Parasitol. 2006 Apr;22(4):143-5
16497558
Br J Haematol. 2006 Nov;135(3):395-404
16989660
J Immunogenet. 1990 Aug-Oct;17(4-5):219-25
2093725
J Biol Chem. 1987 Feb 5;262(4):1596-601
3805045
Nature. 2007 Apr 26;446(7139):1023-9
17460663
Infect Immun. 2007 Jun;75(6):3014-20
17438038
Proc Biol Sci. 2004 May 22;271(1543):1065-72
15293861
Nature. 1990 May 17;345(6272):229-33
2333095
Eur J Biochem. 1995 Dec 1;234(2):616-25
8536711
Nat Rev Immunol. 2007 Apr;7(4):255-66
17380156