Immunochemistry of the Lewis blood-group system: Isolation and structures of Lewis-c active and related glycosphingolipids from the plasma of blood-group O Le(a-b-) nonsecretors

173

238

This review summarizes present knowledge of the chemistry of histo-blood group ABH and related antigens. Recent advances in analytical carbohydrate chemistry (particularly mass spectrometry and NMR spectroscopy) and the introduction of monoclonal antibodies (MoAbs) have made it possible to distinguish structural variants of histo-blood group ABH antigens. Polymorphism of ABH antigens is induced by; (i) variations in peripheral core structure, of which four (type 1, 2, 3 and 4) are known in man; (ii) variation in inner core by branching process (blood group il), leading to variation of unbranched vs. branched ABH determinants; (iii) biosynthetic interaction with other glycosyltransferases (Lewis, P. T/Tn blood systems) capable of acting on the same substrate as the ABH-defined transferases, and finally (iv) the nature of the glycoconjugate (glycolipid, glycoprotein of N- or O-linked type). ABH variants induced by item (i) above have been clearly distinguished qualitatively by MoAbs; e.g., at least six types of A determinants can be distinguished by qualitatively different classes of antibody. The variants induced by item (ii) create mono- vs. bivalent antigens which may be responsible for observed differences in antibody-binding affinity. Detailed studies of the chemistry of these antigens have increased our insight into blood groups, providing the basis for blood group ii and A subgrouping, as well as a relation between the ABH and Lewis, P, and T/Tn systems. A survey of the literature on distribution patterns of ABH variants is presented. It has been assumed that expression of histo-blood group antigens is developmentally regulated. Relationships between histo-blood group expression, development, differentiation and maturation, as well as malignant transformation, are discussed.

Section: Type 1 Chain Abh Antigensmentioning

confidence: 99%

Section: Type 1 Chain Abh Antigensmentioning

confidence: 99%

ABH and Related Histo-Blood Group Antigens; Immunochemical Differences in Carrier Isotypes and Their Distribution

Clausen

Hakomori²

1989

173

238

“…This structure containing both Lec and X antigens is a better inhibitor of the serological reaction of an anti-Lec polyclonal antibody than either of the 2 separate branches alone [49], This suggests that the antisera, defining the Lec negro lacking this enzyme in plasma have been reported. These 2 individuals had the red cell phenotype Le(ab-c-d-) [52].…”

Section: The Lea and Leb Antigensmentioning

confidence: 91%

“…Some recent studies point in this direction. Hanfland et al [49] described a branched oligosaccharide with a nonfucosylated type 1 precursor chain and an X monofucosylated type 2 chain:…”

Section: The Lewis Antigensmentioning

confidence: 99%

Genetics of ABO, H, Lewis, X and Related Antigens

Oriol

Pendu

Mollicone³

1986

The present knowledge on chemical, enzymatic, serologic and genetic aspects of ABH antigens is reviewed in an effort to produce a simple and coherent genetic model for the biosynthesis of these antigens and chemically related structures. The genetic control of type 1 (Le^a, Le^b, Le^c and Le^d), type 2 (X, Y, I, and H), type 3 and type 4 ABH and related antigens in different animal and human tissues is analyzed, taking into account the properties of the glycosyltransferases which are involved in their synthesis and considering possible competition for common acceptor and donor substrates. The phylogeny of ABH determinants shows that they appeared as tissular antigens much earlier than as red cell antigens. The ontogeny of ABH antigens suggests that they behave as differentiation antigens, and an effort is made to correlate their tissular distribution in the adult with the embryological origin of each tissue.

“…Le', Lea, or iactodifucotetraose [7]. The anti-Lea MAb was a generous gift from Dr. W. Young [37], one anti-Leb * The Le' antigen has been reported to be an elongated and branched variant of the basic Galßl^>3GlcNAcß disaccharide with one branch bearing the type 2 chain Le' hapten [9], Two distinct al^2 transferases, encoded by the Secretor and H genes, respectively, are presently believed to exist [2. 18, 26], The Secretor-gene encoded fucosyltransferase has preference for the type 1 chain substrate, whereas the H gene-encoded tranferase has preference for the type 2 chain [3], The Lewis-gene-encoded fucosyltransferase may utilize both the type 1 and type 2 chain substrates, thus participating in the formation of both Le''' ' 1' and Le'A [17].…”

Section: Antibodiesmentioning

confidence: 99%

Lewis Blood Group Antigens in Salivary Glands and Stratified Epithelium: Lack of Regulation of Lewis Antigen Expression in Ductal and Buccal Mucosal Lining Epithelia

Mandel¹,

Ørntoft²,

Holmes³

et al. 1991

The expression of Lewis antigens is thought to be controlled by the Secretor and Lewis genes. While secretor status is known to regulate the expression of ABH antigens in many tissues, few studies have attempted to correlate Lewis antigen expression on erythrocytes and saliva with that of epithelial tissues. We examined the expression of Lewis a and b and related antigens in human epithelium of minor salivary glands and labial nonkeratinized oral mucosae from 16 individuals by immunohistology using monoclonal antibodies. The expression of these antigens, as detected by monoclonal antibodies (MAbs) used, was correlated with erythrocyte phenotype and saliva secretor status. In acinar cells of glands, Le^b antigen was expressed only in secretors, and Le^a only in nonsecretors. However, in gland ducts and oral mucosae, Le^b was found in both secretors and nonsecretors, as well as in 2 cases of Le^a-b-, secretors. Thus, antigen expression in acinar cells of minor salivary glands was correlated with the predicted genotypes, whereas inappropriate expression of Le^b antigen was found in epithelial cells of gland ducts and oral mucosae. The present data indicate that the Lewis blood group phenotype is regulated differently in duct cells and stratified epithelium than in saliva and erythrocytes.