Ia antigenic specificities are oligosaccharide in nature: hapten-inhibition studies.

Abstract

The Ia (I region associated) antigenic system in the mouse is coded for by genes located within the H-2 complex and consists of at least four subregions (IA, IB, IE, AND IC) which code for a minimum of 21 (Ia. 1 to 21) specificities (1-3), although the existence of IB and IE subregions is now being questioned. These antigens were first detected on the surface of B lymphocytes and were subsequently found on macrophages, epidermal cells, and sperm cells (4). It is also apparent that some Ia specificities are present on either resting and activated T-blast cells (2-8). In addition, we have detected considerable amounts of Ia antigenic material in mouse serum and other tissue fluids, particularly after antigenic stimulation (8, 9). The current interest in this system stems from the close involvement of the I region in immune responses (1-3), especially with the recent demonstration that soluble factors of both antigen-specific and nonspecific nature which are involved in T-B cell collaboration (10, 11) and suppression (12), also carry Ia antigens. In this context, we have found that although B cells have a higher density of Ia antigens on their surface than T cells, the Ia antigens in serum are derived from T cells (9).Biochemical studies of the Ia specificities have proceeded along two lines. The cell surface Ia antigens of B cells have been extracted with detergents and were found to be glycoproteins with mol wt of approximately 30,000 (13,14). By contrast, our chemical studies of the serum Ia material suggest that it is predominantly (but not exclusively) carbohydrate in nature as the material has the following properties: (a) It is rich in carbohydrate and almost devoid of protein (15); (b) The Ia antigenicity is destroyed by neuraminidase and periodate, but not by pronase (15); (c) The Ia antigen binds to concanavalin A and Lotus lectins (15); (d) It is extracted and purified from serum by methods identical to those used to prepare oligosaccharides from human milk (15-17); (e) Its behaviour on paper and thin layer chromatography is similar to that of other oligosaccharides (15), and after acid hydrolysis of the purified Ia product a number of simple sugars have been detected by gas-liquid chromatography (manuscript in preparation). In this paper, we describe hapten inhibition studies using a variety of sugars that show that for at least four Ia antigens (Ia.1, Ia.3, Ia.7, and Ia.15) the antigenic specificity is defined by sugars.

Acquisition of murine major histocompatibility complex gene products by schistosomula of Schistosoma mansoni.

“…As indicated by our data, two classes of nonglycolipid molecules, the K and I gene products, can be acquired by schistosomula'as host antigens. Previous work has indicated that the K region product is a glycoprotein of 47,000 mol wt (14), whereas Ia antigens apparently exist either as a cellassociated glycoprotein consisting of two polypeptide chains of about 25,000 and 35,000 mol wt (15) or as soluble low molecular weight carbohydrates (16). Thus, it is clear that host molecules other than glycolipids may associate themselves with the schistosome surface.…”

Culture Filtrate of Cryptococcus neoformans var. gattii (CneF) as a Novel Anti‐Inflammatory Compound in the Treatment of Experimental Septic Arthritis

“…These interactions may play an important role in the activities of phagocytic cells in vivo [38]. In this way, the therapeutic effects of CneF could be due to biochemical characteristics of major (mannan and glucuronic acid) and minor (galactose and xylose) determinants in the molecular structure of CneF components (GXM and GalXM), in which it has recently been shown that yeast cell wall mannans could exert various immunoregulatory properties [39], because D-mannose is often found in mammalian glycoproteins either as a core or end group [40]. Further data indicate that several cytokines such as IL-1a, IL-2 and TNF possess oligomannosyl-speci®c lectin-like speci®city [41±43].…”

“…In the case of the role of the galactose residue in the GalXM molecule, it has been suggested that there are galactose-speci®c lectins on the cell surface of macrophages [38]. Thus, one monosaccharide inhibitor is galactose and sugars related to galactose [40]. Here, the administration of galactose probably interferes with the interaction of galactose-speci®c lectins on the cell surface of macrophages and galactose residues in the molecular structure of type II collagen on the hyaline cartilage of joints [58,59].…”

Incorporation of rat histocompatibility (AgB) antigens into liposomes, and their susceptibility to immune lysis

“…Not only is the distinction from AgB antigens quite clear, but there appears to be a form of the rat Ia molecule which is not retained by ricin lectin either. This is intriguing in view of recent evidence that carbohydrate is implicated as the antigenic determinant of certain mouse Ia antigens [20]. The preparation of liposomes bearing AgB antigens from a mixture of lipids is straightforward.…”