Scand. J. hnmimol.. Vol. 6, 1977. Cellular Distribution, Purification, and Molecular Nature of Human la Antigens D. SNARY, C J. BARNSTABLE, W. F. BODMER, P. N. GOODFELLOW & M. J. CRUMPTON National Institute for Medical Research, Mill Hill, London, and the Genetics Laboratory, Department of Biochemistry, University of Oxford, Oxfr>rd, United Kingdom Snary, D., Barnstable, C. J., Bodmer. W, F., GoodfeMow, P. N. & Crumpton. M. ]. Cellular Distribution, Purificntion, and Molecular NatLire of Human la ,\ntigens. Scand. J. Immunol. 6. 439-452, 1977. i Human la antigens were extensively purified (1390-fold increase in specitic activity) in 32% yield from BRI 8 celts, a lymphobliistoic! B-ccll iinu. l'urilication wasmunimrcd by usinff allogeneic antiseta arising by fiietal-maternal stimulation. The prfKluct, a glycoprotcin fmctinn, contained the la antigens, the M!,A-A and -B antigens, and a glycoproteitl of unknown function. The glycoprotein fraction was cmnpnsed iif four glycosylatcd polypeptides with molecular weights of 43,000, 39,000, 33,000, and 28,000, and j3d-microglobuUn; no polypeptide was linked to another by disiilphide bridges. The A and B antigens oniy were absorbed by antibody against ^^-micro- globulin. The la antigens comprised one each of the 33,000 and 28,000 molecular weight glycosylated polypeptides noncovalently linked together. Thus, only these chains were absorbed by xeni>geneic anti-la antisera and were cruss-Iinked by dimethy!-3-3'-dithic>bispropionimidate dihydrochloridc. The dimeric molecule bound deoxycholate (0.26 g/g of protein) and, when snlubilized in dcnxycholate, has a moiecuhir weight of 77,000. The la allo- and xcno-antigenic activities were labile to heating and proteoiysis and are probably determined by the polypeptide structure. Xenogeneic specific anti-la aniisera were raised in rabbils and mice by immunizing with the giycoproiein fraction. These antisera reacted M'ith B lymphocytes and monocytcs but not T Iymphix:ytes and fibroblasts. Their Fab fragments blocked the cytotoxicity ofthe allogeneic antisera for B lytnphocytes and were piitcnt inhibitors of the mixed lymphf>cyte reaction. M. J. Crimpton, National Institute for Medical Research, Mill Hill. London NW7 lAA, United Kin_edom The major histocompatibility complex of the the HLA-A, -B, and -C loci and is expressed mouse (H-2) and the analogous region of man on essentially all cell types except erythrocytes. (HLA) contain a large nutnber of genes con- These antigens are composed of two non- trolling diverse immune functions, including covalently linked, dissimilar polypeptide chains the regulation of immune responses and (3). One polypeptide has a molecular weight of lymphocyte interactions (I, 2). The gene about 43,000, is glycosylated, carries the products ofthe HLA complex include various serologicaliy defined polymorphic spcciiicitics, complement components and two groups of and is coded by genes in the HLA region polymorphic cell surface antigens (2). One located on chromosome 6 (4, 5). The other group of antigens represents the products of polypeptide is jSg-microglubulin, which has a