Dr. Kalams was the first to demonstrate the persistence of HIV-1 specific cytotoxic T lymphocyte (CTL) clones in vivo during chronic HIV infection, and has received NIH R01-funding to 1) Evaluate why CTL responses decline with disease progression, 2) Assess the T-cell repertoire of developing and established immune responses, and 3) Determine whether the avidity of developing CTL responses influences viral set point. Other research interests include understanding the mechanisms of immune escape from CTL recognition (to evaluate the role HIV sequence variation plays in disease progression), and the evaluation of CTL responses of patients with long-term non-progressing HIV-1 infection (to evaluate whether patients without disease progression have unique or more robust immune responses).

Current active projects include the development of mass cytometry as a platform for evaluation of T cell phenotype and function, and molecular analysis of pathogen-specific T cells. We have developed assays to sort individual T cells, followed by identification of their T cell receptor alpha beta chain usage as well as their transcriptional profile. This allows an in depth evaluation of T cell responses after either natural infection or vaccination.