New findings characterize immune response to HHV-6; advance the field of adoptive immunotherapy
Dr. Louis Flamand’s group has published new details regarding the recognition and presentation of HHV-6 proteins by the immune system. Their work has identified CD8+ T cell viral epitopes derived from the HHV-6B immediate early protein (IE1B) that are then presented by common HLA class 1 alleles.
The article provides evidence for a clear mechanism of proteolytic processing and peptide presentation of the HHV-6B IE1 protein, which is subsequently recognized by specific CD8+ T cells. The group also demonstrates how specific IE1 peptides or “epitopes” are presented for immune recognition by the three most prevalent HLA class I alleles in the Caucasian population, HLA-A*02, HLA-A*03 and HLA-B*07. One such IE1 peptide, conserved between HHV-6A and HHV-6B and presented by HLA-A*02, was found to be capable of generating cytotoxic T lymphocytes (CTLs) capable of killing autologous cells infected with either HHV-6A or HHV-6B.
Defining what constitutes a protective immune response against HHV-6 is crucial for the control of infection in bone marrow transplantation or any conditions where patients are immunocompromised and subject to opportunistic infections (including herpesviruses). Baylor College of Medicine’s Center for Cell and Gene Therapy has demonstrated a way to quickly generate antiviral T cells for the treatment of opportunistic viral infections, and recently reported success in a small clinical trial (Papadopoulou 2014). This technique offers many advantages over conventional antiviral treatment options because there is no toxicity and it can be used for patients infected with strains that are resistant to commonly used antivirals. Unfortunately, the cells themselves have historically been complex to prepare and limited in their antiviral range.
While T cell immunotherapy can successfully control cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivations in BMT patients, this technique has not yet been optimized for managing HHV-6 infections, in part due to a lack of identified protective CD8+ T cell epitopes. The findings presented in this recent report from Dr. Flamand’s group will help advance this field, providing key steps toward the effective treatment and/or prevention of HHV-6 reactivation in BMT recipients.
For more information, read the full paper.