Vaccine and Infectious Disease Division

Characterizing the immune response to HSV-2

Recent work has suggested that a certain kind of immune cell, CD8+ T cells, is important in keeping the chronic infection by herpes simplex virus 2 (HSV-2) in check in the body.  These cells adapt to recognize a given pathogen and then can target and kill human cells infected with that pathogen.  CD8+ T cells specific to a foreign invader generally recognize just one piece of one protein from that pathogen, also known as an epitope.  To recognize these antigens presented on the surface of infected cells, CD8+ T cells develop a specific kind of receptor (T cell receptors, or TCRs) on their cell surface that is chosen from an extremely wide range of billions of genetic possibilities.

To get a better picture of the characteristics of HSV-2-specific CD8+ T cells in humans, VIDI affiliate investigator Dr. David Koelle and colleagues looked at the TCR variants chosen by these cells in five HSV-2 positive people with T cells specific to a single HSV-2 epitope.  Despite the wide range of choices available for TCR selection, the researchers found that the HSV-2-specific CD8+ T cells from these individuals tended to select the same few variants of TCR genes. 

This phenomenon implies that evolutionary pressure has optimized the choice of just a few TCR sequences out of a huge range of possibilities.  These optimal genes have been shown to be associated with favorable outcomes in non-human primate models of HIV/AIDS, and are known to occur in chronic human infections with body-wide infection of specialized cells that are especially good at interacting with T-cells.  The new data show that even HSV, which infects only local areas of skin cells and neurons, can also, over time, stimulate these highly focused T-cell responses. The TCR genes identified in this study may be useful in future T-cell therapies or vaccines for HSV infections.

Public TCR Use by Herpes Simplex Virus-2-Specific Human CD8 CTLs.  Dong L, Li P, Oenema T, McClurkan CL, Koelle DM.  J Immunol. 2010 Feb 5.