Vaccine and Infectious Disease Division

Probing T cell responses to HIV

Among the myriad challenges to creating an effective HIV vaccine, the virus’ genetic diversity is one of the biggest. Any vaccine that will protect a majority of the population will have to elicit a broad range of immune responses to ensure the recognition of all or most strain variants. Current searches for HIV vaccines focus on candidates that may elicit broad T cell responses. To assess the capacity of these immune cells to recognize a broad range of HIV peptides, researchers led by Virginia Mason Medical Center physician Dr. Uma Malhotra and VIDI co-director Dr. Julie McElrath examined the breadth of virus epitope variants recognized by T cells from people newly infected with HIV and from people who had received a candidate HIV vaccine.

The scientists isolated T cells from these two groups of people and probed the cells’ ability to respond to a variety of HIV peptides, including those from quickly mutating regions of the HIV genome.  In these analyses the researchers took into context the infecting virus sequence in the infected people and the vaccine sequence in the vaccine recipients. They found that while cells from both groups were able to recognize and respond to a similarly broad range of HIV peptide variants, their responses were not always robust to peptides that varied from the infecting virus or the vaccine sequence by one or more amino acids. This study differed from past studies of how T cells recognize HIV peptides in that Malhotra and colleagues used a set of peptides that included naturally occurring variants from HIV proteins, while past studies only looked at the most common, or consensus, sequence for each peptide.

Functional properties and epitope characteristics of T-cells recognizing natural HIV-1 variants.  Malhotra U, Nolin J, Horton H, Li F, Corey L, Mullins JI, McElrath MJ.  Vaccine. 2009 Sep 9.