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 evoluti onary novel immunogenic carbohydrate antigen in mice. The or-gal epitope (G al alpha1-3Gal beta1-4GlcNAc-R) is an autoantigen, abundantly expressed in wild type mice, but absent in alpha1,3galactosyltransrerase knock-out (KO) mice, where it can induce the production of the anti-Gal antibody. Hybridom a clones secreting anti-Gal were isolated from different mice and their imm unoglobulin genes were analyzed. All anti-Gal clones were found to be encod ed 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 encode d 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 div ersity and somatic mutations can generate new antibodies that have not been produced in the course of the evolution of a species. (C) 2000 Elsevier Sc ience Ltd. All rights reserved.