Peptide epitope binding specificity and V K and V H gene usage in a monoclonal IgM natural autoantibody to T cell receptor CDR1 from a viable motheaten mouse.

Abstract

Autoantibodies (AAbs) to T cell receptor (TCR) determinants are produced in humans during the course of rheumatoid arthritis and systemic lupus erythematosus as well as in retroviral infections. We have examined the binding specificity of a panel of monoclonal antibodies derived from mutant viable motheaten (mev) mice against several TCR peptide determinants representing the complementary determining region 1 (CDR1) regions of various Vbeta families, and have identified one mAb, UN37-5, that shows high affinity binding with specificity for two CDR1 peptide determinants. The light and heavy chain V genes of UN37-5 were sequenced and compared to known V genes. The UN37-5 V H gene sequence represents the V H J6O6 family and is most similar to a previously reported V H gene derived from a germ line DNA fragment representing a unique J606 family V H gene. This germ line V H gene is also used by previously characterized mev derived mAbs directed against thymocyte and RBC antigens. The UN37-5 V L gene sequence represents the V K 4/5 gene family. It has 87% homology with the V K Ox-1 germline gene. The UN37-5 V K sequence has greater than 95% identity at the amino acid level with VK L chains from IgM hybridomas specific for DNA and the influenza virus hemagglutinin. The specificity of this AAb is determined by the V H CDR3 and a V K chain which has not been utilized in previously reported mev autoantibodies.