Histochemical and Cytochemical Localization of Blood Group Antigens N.lTo . T. HIROTA

With 20 Figures and 7 Tables

)! SEMPER

~

GUSTAV FISCHER VERLAG· STUTTGART· NEW YORK· 1992

NOBUAKI ITo, Ph.D. TADAOMI HIROTA, MD, Ph.D. Department of Legal Medicine, Nara Medical University, Kashihara Nara 634 Gap an)

Acknowledgements The authors wish to thank Dr. Shingo Kawahara, Dr. Mitsuru Nakajima* and Dr. Yoshiro Okamura (Departments of Legal Medicine and *Pediatrics, Nara Medical University) and Prof. Katsuji Nishi (Department of Legal Medicine, Shiga Medical College) for their help and encouragement during this study. This work was supported in part by the Cooperation Research Program of the Primate Research Institute of Kyoto University.

Die Deutsche Bibliothek - CIP-Einheitsaufnahme

Ito, Nobuaki: Histochemical and cytochemicallocalizatiort of blood group antigens : with 7 tables / N. Ito ; T. Hirota. - Stuttgart; New York; Jena : Fischer, 1992 (Progress in histochemistry and cytochemistry; Vol. 25, No.2) ISBN 3-437-11460-3 NE: Hirota, Tadaomi:; GT

Library of Congress Card-No. 88-20469

Published jointly by: Gustav Fischer VerlagNCH Publishers 220 East 23rd Street, Suite 909, New York, New York 10010 Gustav Fischer Verlag Wollgrasweg 49, D-7000 Stuttgart 70 (Hohenheim) FRG © Gustav Fischer Verlag· Stuttgart· Jena . New York· 1992 Alle Rechte vorbehalten Gesamtherstellung: Laupp & Gobel, NehrenlTiibingen Printed in Germany

Contents 1

2 2.1

2.2 3 3.1

3.2 3.3 3.4 4 4.1

4.2 4.3 5 6 7 7.1 7.2 8

8.1 8.2 8.3 9 10

10.1 10.1.1 10.1.2 10.1.3 10.2 11 11.1 11.2 11.3 12 12.1

Introduction. . . . . . . . . . . . . . . . . . . . . . Structures of blood group ABH and related antigens Determinant structures of ABH and related antigens Back bone structures carrying the blood group determinants . Genetics and biosynthesis of blood group antigens The H and the Se gene. The ABO gene The Lewis gene . . . . The X gene . . . . . . Distribution and regulation of blood group antigens in human tissues Distribution and regulation of the Type 1 and Type 2 chain antigens . Distribution of the type 3 and type 4 chain antigens . . . . . . . . . . Effects of AIAz subgroup on the expression of blood group antigens. Mosaic distribution pattern of blood group antigens and cell maturation. Lectins and their blood group specificity. Blood group related reactivity of lectins Blood group ABH specific lectins . . . . Precursor-specific lectins . . . . . . . . . Differential abilities in the recognition of ABH antigens among blood group-specific lectins and monoclonal antibodies Blood group A specific lectins Blood group B specific lectins . . . . . . . . Blood group H specific lectins . . . . . . . . Blood group-nonrelated reactivity of lectins . Histochemical determination of the carbohydrate structures of blood group and related substances . . . . . . . . . . Analysis of carbohydrate chain in the pancreas Binding sites of soybean agglutinin. . . . . . . Binding sites of peanut agglutinin . . . . . . . Analysis by immunostaining with monoclonal antibodies Analysis of carbohydrate chains in submandibular glands. Subcellular distribution of blood group antigens Golgi complex. . Mucous granules . . . . . . . . . . . . . . . . . Nucleus . . . . . . . . . . . . . . . . . . . . . . Malignant and developmental changes in blood group antigens . Changes in the expression of blood group antigens during embryogenesIs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..

1

2 3 5 8 9 10 11 12 12 16 21

22 23 26

29 29 30 31

33 34 34 35 37

38 38 42 43 46 50 50 51 55 57 57

VI . Contents

12.2 12.2.1 12.2.2 12.2.3 12.2.4 13 13.1 13.2 14

Aberrant expression of blood group antigens in malignant cells . . . . . Deletion of the ABH antigens, accumulation and modification of precursors . . . . . . . . . . . . . . . . . . . . . . . . . . Accumulation ofT and Tn antigen . . . . . . . . . . . Neo- or oncofetal expression of blood group antigens Incompatible expression of blood group antigens . . . Evolution of blood group antigens . . . . . . . . . . . Evolutionary changes in the pattern of expressions of ABH antigen in tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Relationship between lectin binding properties and the expression of ABH antigens in vascular endothelia and red blood cells Summary and conclusion References . . Subject index . . . . . .

58 58 59 61

62 62 64 ·64 66

69 83

1 Introduction The antigenic determinants of blood group ABH and related antigens reside in the terminal portion of carbohydrate side chains of glycoproteins and glycolipids (WATKINS 1966, 1978, 1980). They are widely distributed throughout human and animal bodies, especially in epithelial tissues and in their secretions. Recent phylogenic studies show that the ABH antigens appear earlier in vertebrate evolution in ectodermal or endodermal tissues than do mesenchmal hematopoietic tissues (ORIOL et al. 1986) and that the expression of ABH antigens in erythrocytes and endothelial cells is confined to human and some higher primate species (ITo et al. 1990 b; ORIOL et al. 1984, 1987; SOCHA et al. 1987). Thus, the term «blood group antigen» is not necessarily adequate for these substances. Considering these circumstances, the term «histo-blood group antigens» has been proposed for the ABH, Lewis and related carbohydrate antigens (CLAUSEN and HAKOMORI 1989). The ubiquitous presence of the blood group antigens in vertebrate species may indicate the importance of these substances, although their physiological role(s) has not yet been disclosed. By the 1960s, chemical structures of ABH and Lewis blood group antigens had been determined and a precursor-endproduct relationship established between H, A or B, and Lewis a and b antigens (WATKINS 1966, 1987, 1980). This led to an understanding of the biosynthetic pathways and basic genetics of the system. Histological mapping of the ABH antigens was also carried out extensively and the distribution of the antigens in human tissues was largely established (SZULMAN 1960, 1962). In addition, changes in expression during normal differentiation and malignant transformation have been investigated in various tissues (SZULMAN 1964, 1971; DAVIDSOHN 1972). The findings obtained by these studies have led to the development of an important concept that blood group and related antigens are onco-developmental antigens in human tissues. Recent progress in biochemical, physicochemical and immunochemical methods has amplified our knowledge about the chemical structures of blood group antigens. Thus it was demonstrated that the same determinant structures can be carried on many different types of core saccharide structures; in addition, a large variety of carrier isotypes have been found (CLAUSEN and HAKOMORI 1989). These carrier isotypes exhibit fine differences in antigenicity which can be discriminated specifically only by certain monoclonal antibodies (MAbs) (FEIZI 1985; FEIZI and CHILD 1987). It is therefore necessary to re-evaluate the previous histochemical findings by using recently developed reagents and procedures. In fact, dramatic progress has been brought about in" histochemical studies of blood group-related antigens by the introduction of MAbs as well as by the development of indirect immunoperoxidase methods. Through these studies, it has become evident that the mechanism of biosynthesis and regulation of blood group-related antigens in different types of cells and tissues is not so simple as previously supposed. Of course, MAbs as recognizing reagents for specific sugars and oliogasaccharides are most powerful tools in the histochemical analysis of carbohydrate antigenic structures.

2 . N. Ito . T. Hirota

However, independent use of these reagents provides information only about a peripheral portion of antigenic structures. It is now realized that analysis of the core saccharide structures in individual cells and tissues is indispensable for understanding the mechanism of biosynthesis and regulation of these substances. For this purpose, combined use of other reagents such as lectins and glycosidases is required. Although the purpose of this article is to review in depth the recent progress in histoand cytochemical studies of the blood group antigens, special emphasis will be placed on the usefulness and limitation of lectins as tools for localization and analysis of the blood group antigens in tissue sections. In spite of the fact that many of the lectins usually employed exhibit blood group and precursor specificities (GOLDSTEIN and PORETZ 1986; Wu and SUGn 1988), they have not been properly appreciated as useful histochemical reagents for such purposes. Emphasis will also be put on the importance of combined use of glycosidase digestion procedures using lectin histochemistry and immunocytochemistry using MAbs. Introduction of glycosidase digestion procedures makes it possible to analyze the chemical structures of carbohydrate chains in histochemical systems just as in biochemical systems. Owing to successful application of these reagents, histochemical localization and analysis of the blood group antigens are becoming one of the most reliable and advanced field of carbohydrate histochemistry. The development of this field may lead to a more widely applicable method being developed for in situ chemical analysis of carbohydrate structures. Along with the development of histochemical analytical methods, lectin-gold or immuno-gold staining procedures have been successfully introduced into ultrastractural localization of these substances. The findings obtained by these studies are essential to understanding the mechanisms of biosynthesis and carbohydrate chain processing in different cell types. Since knowledge about the chemical structures and biosynthetic pathways of the blood group antigen is a prerequisite for shedding light on the problem of the localization and analysis of these antigenic structures, we will briefly summarize the recent biochemical and genetic knowledge of these substances in the following two Chapters. We will then proceed to, describe the distribution of the antigens and the regulation of their synthesis (Chapter 4-5), blood group specificity of lectins and their use in the histo- and cytochemical detection of the antigens (Chapter 6-9), histochemical analysis of carbohydrate chains (Chapter 10), subcellular localization of antigens (Chapter 11), changes during differentiation and malignant transformation (Chapter 12), and finally, the evolutionary aspects of the antigens (Chapter 13).

2 Structures of blood group ABH and related antigens Although A and B antigens were originally detected on erythrocytes, chemical analysis of antigenic substances from erythrocytes has been unsuccessful until recently. Since

Localization of blood group antigens . 3

antigenic substances on erythrocytes are firmly bound to membrane, it was difficult to isolate them with water or salt solution and the amounts obtained by extraction with ethanol were very small indeed (WATKINS 1966). Consequently, studies on the chemical structures of the antigenic determinants were performed on water-soluble glycoproteins isolated from secretions, primarily from ovarian cyst fluid and milk oligosaccharide. These sources contain relatively large amount of the antigenic substances. The structures of principal antigenic determinants of the ABH and their related antigens have been thoroughly investigated by MORGAN and WATKINS, KABAT and associates, and ISEKI et al. (ISEKI 1977; KABAT 1982; WATKINS 1966, 1978, 1980). Definite antigenic structures of ABH and Lewis a and Lewis b antigens were determined in the 1960s.

2.1 Determinant structures of ABH and related antigens ABH and related antigens are oligosaccharides. These antigenic structures are determined by the composition and sequence of monosaccharide constituents. Figs. 1 and 2 illustrate monosaccharide constituents of blood group related antigens and the chemical

H3 ~

OH

0 HOH OH'

L - FUCOSE

OH

;~:' ~H

.OH

N - ACETYL-D-GALACTOSAMINE

NHCOCH 3

:~:' ~H.OH HOCH 2

D-GALACTOSE

OH

CO\jH .OH

O~

N - ACETYL-D-GLUCOSAMIN E

NHCOCH 3

Fig. 1. Monosaccharide constituents of carbohydrate determinants of blood group-related antigens.

4 . N. Ito' T. Hirota

GaINAc(cx1-3) -Gal (81-3, 4) -GIcNAc

A antigen

I

Fuc(cx1-2) Gal(cx1-3) -Gal (81-3, 4) -GIcNAc

B antigen

I

Fuc(cx1-2)

Gal (81-3, 4) -GIcNAc

H antigen

I

Fuc(cx1-2) Gal(81-3)-GIcNAc

. L ea antIgen

I

Fuc(cx1-4) GaI(81-3) -GIcNAc I

. Le b antIgen

I

Fuc(cx1-2) Fuc(cx1-4)

Gal (81-4) -GIcNAc

. Le X antIgen

I

Fuc(cx1-3) Gal(81-4)-GIcNAc

LeY antigen

I

Fuc(cx1-2) Fuc(cx1-3) Fig. 2. Oligosaccharide structures of blood group ABH and Lewis-related antigens. Fuc = Lfucose, GalNAc = N-acetyl-D-galactosamine, Gal = D-galactose, GlcNAc = N-acetyl-D-glucosamme.

structure of ABH, Lewis a (Lea), Lewis b (Leb), Lewis x(Le X) and Lewis y(LeY) antigens respectively. The minimum immunoreactive structure of the blood group H antigen is the disaccharide Fuc-(a 1-2)-Gal-R, which is a precursor of the A-and B-active trisaccharide Ga1NAc-(a1-3) - [Fuc-(a1-2)]-Gal-R and Gal-(a1-3)-[Fuc-(a1-2)]-Gal-R (where R is the carbohydrate or carbohydrate chain) respectively (WATKINS 1966). These are carried by both type 1[Gal-(~1-3)-GlcNAc] and type 2[Gal-(~1-4)-GlcNAc] precursor chains, while Lea and Le b antigens are only carried by type 1 chain. LeX and LeY antigenic determinants which are positional isomers of Lea and Le b antigens are carried by tpye 2 precursor chains.

Localization of blood group antigens . 5

2.2 Backbone structures carrying blood group determinants Owing to the recent development of various analytical methods such as application of exo-and endoglycosidase, micro-methylation, mass spectrometry, and monoclonal antibodies, it has been possible to analyze the detailed structures of glycosphingolipid isolated from red blood cells (HAKOMORI 1981, 1984). In contrast to the glycoprotein antigens, which show a great deal of heterogeniety (KABAT 1982), products isolated and purified from erythrocyte membrane are homogeneous, allowing precise and detailed structures to be determined. These studies show that blood group antigens of glycolipids in erythrocyte membrane are carried by branched and unbranched type 2 chains of varying chain length. Repeating N-acetyl lactosamine (Gal~I-4GlcNAc)n structure as well as branching structure (both carrying antigenic determinants) are recognized by cold agglutinin and express i and I antigens respectively (FEIZI 1981). These type 2 chain antigens and their unsubstituted core structures expressing i and I antigens are also carried by intrinsic proteins of human erythrocytes such as the Nglycosidically linked carbohydrate chain (FUKUDA et al. 1984). As described in Chapter 3.3, type 1 blood group antigens are minor components of red blood cells. They are not integral parts of red blood cell membranes but absorbed from the serum (CLAUSEN et al. 1985a; MARCUS and CASS 1969). In addition to differences in the branching and elongation status of type 2 precursor chains, new series of blood group glycolipid antigens have been identified by the introduction of monoclonal antibodies that recognize specific A and H determinants with specific combinations of carrier carbohydrate chains, i.e. type 3 and type 4 carrier chains (Fig. 3). Antigens carried by both type 3 and type 4 carrier chains are found exclusively on erythrocytes of At individuals but not those of A2 individuals (CLAUSEN et al. 1984, 1985b, 1987). The precursor of type 3 chain A, i.e. type 3 chain H, was detected in A2 erythrocytes and in much smaller amounts in At erythrocytes, but it was absent in both 0 and B erythrocytes (CLAUSEN et al. 1985b). Type 4 chain A(globo-A) and H(globo-H) antigens are the minor components of antigens in At and 0 erythrocytes, respectively (CLAUSEN et al. 1984). Thus, At and A2 erythrocytes can be qualitatively discriminated by the presence and absence of type 3 and 4 A antigens in addition to quantitative difference in type 2 based antigens. Probably type 4 chain A or H antigens are only present in P t P2 individuals since the internal core globoside has been identified as a P blood group antigen (CLAUSEN et al. 1987; see Table 1). Type 3 A antigen is essentially an extension of a type 2 chain, the antigen being constructed by the attachment of A antigenic trisaccharide determinant to the terminal GalNAc residue of type 2 A antigens i.e. repetitive A antigens. Thus it should be discriminated from O-glycosidically linked type 3 A antigen, which was found in ovarian cyst fluid and saliva (DONALD 1981), although their antigenicities may be similar to a certain extent (see section 4.2). O-glycosidically linked type 3 H antigens were demonstrated in a glycoprotein isolated from blood group 0 erythrocytes (TAKASAKI et

6 . N.lto . T. Hirota

GaINAc( al-3) -Gal( (31-3) -GaINAc(a 1-3) -Gal «(31-4)I

Fuc(al-2)

Fuc(al-2)-

Gal «(31-3) -GaINAc( al-3) -Gal «(31-4)I

Fuc(al-2)

Type 3 A antigen

I

Type 3 H antigen

I

Fuc(al-2)

GaINAc( al-3) -Gal «(3 1-3) -GaINAc(3-

Type 4 A antigen

I

Fuc(al-2)

Gal((3 1-3) -GaINAc(3-

Type 4 H antigen

I

Fuc(al-2)

Fig. 3. Structure of type 3 A, H and type 4 A, H antigens.

al. 1978). B active variants of type 3 and 4 chain have not yet been reported for erythrocyte membrane. Recent biochemical studies of glycoprotein antigens in various tissues have also demonstrated the great amount of complexity and polymorphyism of blood-grouprelated carbohydrate chains that has been reported in glycolipid antigens. A series of branched and unbranched structures of varying chain length has been reported to occur in gastric mucins (HOUNSELL and FEIZI 1982; SLOMIANY et al. 1984), large and small intestine (PODOLSKY 1985), cervical mucin (YUREWICZ et al. 1982), bronchial mucins (BERG et al. 1987), ovarian cyst fluids and saliva (DONALD 1981) and seminal plasma mucin (HANISCH et al. 1986). These all contained both type 1 and type 2 structures, carried by O-linked glycoproteins. Recently, polyfucosylated N-linked glycoproteins with blood group specificity have been isolated from human small intestinal epithelial cells (FINNE et al. 1989). The blood group determinant of N-linked glycoprotein was mainly type 2, whereas glycolipid from the same cells contained mainly type 1 determinants (BJORK et al. 1987). Thus, except for a core portion of saccharide chains in the vicinity of protein or lipid molecules, it becomes evident that blood group antigens can be carried by different types of glycoconjugate species, i.e. by both N- and O-linked glycoproteins and glycosphigolipids which are widely distributed in various tissues and

Localization of blood group antigens . 7

may play different roles in the tissue (CLAUSEN and HAKOMORI 1989). These carbohydrate sequences may be synthesized by common glycosyltransferases (PAULSON and COLLEY 1989). Table 1 illustrates the fundamental structures of glycoconjugate carrying the blood group determinants. They are composed of three different moieties, i.e. carrier protein or . glycosphingolipid, carbohydrate chain extending from glycosylation sites (inner core) and the peripheral disaccharide (peripheral core) serving as actual precursor struc-

Table 1. Fundamental structures of glycoconjugates carrying the blood group antigens. Peripheral core

Inner core

Glycoconjugate species

Type 1

Repeating':' or branching,f* N -acetyllactosamine

N -linked and O-linked Glycoprotein

Complex and hybrid type (N-linked glycoproteins)

Glycosphingolipid

Gal~1-3GlcNAc~-

Type 2 Gal~l-4GlcNAcf3--

Type 3 A associated Gal~1-3GalNAcal-3Gal~-

I

Fucal-2 A

O-linked Glycoprotein

Type 3 Simple Mucin Type

T

Gal~1-3GalNAcal-

Tn Type 4

Glycosphingolipid

Gal~1-3GalNAc~1-

3Galal-4Gal~1-4Glc~1-

p

pk Globoside (P) ~. (Gal~l-4GlcNAc)n,

'f':,

Gal~l-6

"GlcNAc

Gal~l-4

/

8 . N. Ito . T. Hirota

ture for various glycosyltransferases, including most blood group-related transferases (which terminate the chain elongation process) (CLAUSEN and HAKOMORI 1989).

3 Genetics and biosynthesis of blood group antigens The inheritance of ABO(H) and Lewis blood types, and hence the ability to produce these antigenic structures is controled by four independent genetic loci, i.e. the ABO, the Lele, the Hh and the Sese loci. Table 2 shows the relationship between genotype and phenotype for blood group antigen expression in red blood cells and saliva. As described in Chapter 4.1, the relationship between genotype and the pattern of expression of these antigens in many epithelial tissues is essentially similar to that in the saliva. However, in some cells and tissues, patterns of the expression of these antigens are not consistent with the genotype deduced from the expression of these antigens in red blood cells and saliva (Chapter 4.1). As can be seen, the H gene is indispensable for the expression of ABH antigen on red blood cells, whereas the Se gene is required for the expression of ABH, Leb and LeY antigens in secretions. The expression of Leb antigen on red blood cells is also required for the presence of the Se gene. In persons who do not have H gene (the hh genotype) and belong to the rare Bombay blood group, no ABH antigen is detected in red blood cells even though they possess A and/or B genes. On the other hand, persons who lack the Se gene and are se/se homozygous (nonsecretors) cannot secrete these antigens in Table 2. Relationship between genotype and phenotype of blood group antigens on erythrocytes and secretions. Phenotype

Genotype

Saliva

Erythrocytes

ABO, ABO, ABO, ABO, ABO, ABO, ABO, ABO,

H, Se, Le H, Se, Ie H, se, Le H, se, Ie h, Se, Le h, Se, Ie h, se, Le h, se, Ie

ABH Lea

Leb

+ + + +

+

Lex

LeY

ABH Lea

Leb

-*

+ +

+

+ + +

+ +

+ + +

Lex

+ + (+) (+)

LeY

+ + (+)** (+)

°

* Although MAbs-LeY which cross-react with type 2 H antigen preferentially agglutinated erythrocytes, more specific MAbs-LeYwere unable to agglutinate erythrocytes (FURUKAWA et al. 1990).

**

Not yet tested.

Localization of blood group antigens . 9

their secretions. Most people (75-80%) are secretors whose genotype are Se/Se or Se/se and do secrete these antigenic substances in their secretions. The blood group ABH and related antigens are carbohydrates and hence they are secondary products of the blood group genes. The antigenic structures of these antigens are constructed by the stepwise addition of the specific monosaccharide and each step is catalyzed by the specific sugar transferase that is encoded by the gene. Thus, these antigens are the interaction products of different genes; they are produced by the sequential action of the different specific sugar transferase coded by the different genes on the common precursors. The addition of a single monosaccharide to a given kind of carbohydrate chain results in the masking of the antigenicity of the substrate carbohydrate structure and confers new antigenicity to newly produced sugar chains. As deduced from the structure of ABH and related antigens (Chapter 2), the structure of H antigen is a prerequisite for the production of AB, Leb and LeY antigens. In other words, H antigen is a common precursor for these antigens. Although Lea and LeX antigens are also supposed to serve as a precursor for Leb and LeY antigens respectively, such a relationship had never been demonstrated in human tissues. Hence, transfer or aFuc to terminal Gal residues of precursor chains is a key step in the expression of these antigens. The step is catalyzed by the enyzme,a-2-L-fucosyltransferase. Fig. 4A and B illustrates the biosynthetic pathways of type 1 and type 2 based blood group antigens, respectively.

3.1 The H and the Se gene a-2-L-Fucosyltransferase for the formation of H antigen is coded by the H gene. Its alleic gene h is a silent gene and does not code for the enzyme. The Se gene was assumed to be the regulator gene which controls the expression of the H gene for'producing a-2L-fucosyltransferase in epithelial tissues, while the Z gene regulates the expression of H gene on erythrocytes (WATKINS 1966, 1978, 1980). Recently, however ORIOL et al.

Gal(el-3)-GlcNAce-R

Type 1 A(B) antigen

Type 1 H antigen

Type 1 precursor SetH) gene

--+

Gal(el-3)-GlcNAce-R

A(B) gene

--+

I

1

1

Gal( 151-3) -GlcNAce-R I

Fuc(O!I-li) Lea antigen

Le gene

Gal(el-3)-GlcNAce-R I

I

Fuc(0!1-2)

Fuc(0!1-2) Le gene

GaINAc(GalJ(0!1-3)-Gal(el-3)-GlcNAce-R

I

Fuc(0!1-2) Fuc(O!I-li) Le b antigen

Fig.4A. Biosynthetic pathways of type 1 chain structures.

1

Le gene

GaINAc( Gal) (0!1-3)-Gal (15 1-3)-GlcNAce-R I

Fuc(0!1-2) Fuc(O!I-li) ALeb(BLeb ) antigen

10 . N.lto . T. Hirota

Gallal-4)-GlcNAca-R

Type 2 A(B) antigen

Type 2 H antigen

Type 2 precursor H(Se) gene ~

Gal(al-4)-GlcNAca-R

A(B) gene ~

I

1

I

Fuc(al-2)

1

X gene

Gal (al-4) -GIcNAca-R I

Fuc(al-3) Lex antigen

Fuc(al-2) X gene

Galla 1-4) -GIcNAca-R I

GaINAc(Galj(al-3)-Gallal-4)-GlcNAca-R

I

Fuc(al-2) Fuc(al-3) LeY antigen

1

X gene

GaINAc( Gal) (a 1-3) -Galla 1-4) -GlcNAca-R I

I

Fuc(al-2) Fuc(al-3) ALe Y (BLe Y ) antigen

Fig. 4B. Biosynthetic pathways of type 2 chain stru(GlcNAc~1-4GlcNAc)t_3

a-Fuc a-Fuc

GlcNAc~1-4GlcNAc>Fucal-2Gal~1-4GlcNAc

GalNAcal-3GalNAc> a-GalNAc a-GalNAc GalNAcal-3GalNAc> aGalNAc GalNAcal-3Gal=aGalNAc a-GalNAc a-Gal a-GalNAc, a-Gal a/~-GalN Ac > a/~-Gal a-Fuc a-Fuc

Abbreviations: GalNAc: N-acetyl-D-galactosamine; GlcNAc: N-acetyl-D-glucosamine; Gal: D-galactose; Fuc: L-fucose.

GSAI-B4 GSA-I SJA AAA GTA CSA LTA UEA-I UEA-II GSA-IV GCA ECA PNA SBA VVA-B4 GSA-II

GSAI-~

Source

Lef:tins

Specificity Human ABO (H) blood group Sugar

Table 4. Blood group and sugar specificity of lectins.

.:

t-l :::r:: ::;. o

8

>-

Histochemical and cytochemical localization of blood group antigens.

The oligosaccharide structures of blood group antigens are not the primary gene products; they are constructed in a stepwise manner by adding particul...
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