Genes coding evolutionary novel anti-carbohydrate antibodies: studies on anti-Gal production in alpha 1,3galactosyltransferase knock out mice.
This study analyzes the gene repertoire coding for antibodies to an evolutionary novel immunogenic carbohydrate antigen in mice. The alpha-gal epitope (Gal alpha 1-3Gal beta 1-4GlcNAc-R) is an autoantigen, abundantly expressed in wild type mice, but absent in alpha 1,3galactosyltransferase knock-out (KO) mice, where it can induce the production of the anti-Gal antibody. Hybridoma clones secreting anti-Gal were isolated from different mice and their immunoglobulin genes were analyzed. All anti-Gal clones were found to be encoded by the heavy chain gene VH22.1 and light chain gene VK5.1. Moreover, one 'forbidden' anti-Gal clone, produced in a wild type mouse, was also encoded by VH 22.1 and VK 5.1. The genes coding for the different anti-Gal clones were found to contain somatic mutations and different CDR3 domains. These data imply that a highly restricted gene usage combined with junctional diversity and somatic mutations can generate new antibodies that have not been produced in the course of the evolution of a species.
Chen
Z C
ZC
Department of Cardiovascular-Thoracic Surgery, Rush University, 1653 West Congress Parkway, Chicago, IL 60612, USA. zchen@rush.edu
Radic
M Z
MZ
Galili
U
U
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D000915:Antibody Affinity / Q000235:genetics / Q000276:immunology; D000916:Antibody Diversity / Q000235:genetics / Q000276:immunology; D000918:Antibody Specificity / Q000235:genetics / Q000276:immunology; D002240:Carbohydrate Sequence; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D019143:Evolution, Molecular; D005690:Galactose / Q000276:immunology*; D005700:Galactosyltransferases / Q000172:deficiency* / Q000235:genetics; D005803:Genes, Immunoglobulin / Q000235:genetics* / Q000276:immunology; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D003165:Complement System Proteins; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase; D005690:Galactose