CTLA-8, CLONED FROM AN ACTIVATED T-CELL, BEARING AU-RICH MESSENGER-RNA INSTABILITY SEQUENCES, AND HOMOLOGOUS TO A HERPESVIRUS SAIMIRI GENE

To detect novel molecules involved in immune functions, a subtracted c DNA library between closely related murine lymphoid cells was prepared using improved technology. Differential screening of this library yie lded several clones with a very restricted tissue specificity, includi ng one that we named CTLA-8. CTLA-8 transcripts could be detected only in T cell hybridoma clones related to the one used to prepare the lib rary. Southern blots showed that the CTLA-8 gene was single copy in mi ce, rats, and humans. By radioactive in situ hybridization, the CTLA-8 gene was mapped at a single site on mouse chromosome 1 A and human ch romosome 2q31, in a known interspecific syntenic region. The CTLA-8 cD NA sequence indicated the presence, in the 3'-untranslated region of t he mRNA, of AU-rich repeats previously found in the mRNA of various cy tokines, growth factors, and oncogenes. The CTLA-8 cDNA contained an o pen reading frame encoding a putative protein of 150 amino acids. This protein was 57% homologous to the putative protein encoded by the ORF 13 gene of herpesvirus Saimiri, a T lymphotropic virus. These findings are discussed in the context of other genes of this herpesvirus homol ogous to known immunologically active molecules. More generally, CTLA- 8 may belong to the growing set of virus-captured functionally importa nt cellular genes related to the immune system or to cell death and ce ll survival.