Trypanosome Surface Antigen Genes: Analysis Using Recombinant DNA

摘要

The objective of this project is to identify and isolate early (frequently expressed) variant antigenic types (VATs), and clone and characterize their expressed variant surface glycoprotein (VSG) genes. Numerous syringe passaged and cyclically transmitted, frequently expressed VATs have been isolated, monoclonal antibodies prepared to their VSGs, and the expressed VSG genes have been cloned. We have shown that many diverse stocks express VSG epitopes related to the early IsTat epitopes. The VSG gene organization has been characterized. We have confirmed sequence homology at the 3' terminus of the VSG genes and have discovered additional homology near the 5' terminus of unrelated VSG genes. Numerous relapse VATs have also been isolated and characterized with respect to telomeric location of VSG genes and duplicative or non-duplicative mode of VSG gene expression. We have found that two fundamental processes control the expression of VSG genes. One involves gene duplication; the other telomeric activation. In addition, the telomeric location of the gene affects its probability of expression and stability. DNA sequence analysis in and around flanking VSG genes has characterized some of the internal homology and identified flanking sequence homology blocks. The latter probably function in duplicative activation of VSG genes. Keywords: African trypanosomes, sleeping sickness.