COMPASS is a statistical framework that enables unbiased analysis of antigen-specific T-cell subsets. COMPASS uses a Bayesian hierarchical framework to model all observed cell-subsets and select the most likely to be antigen-specific while regularizing the small cell counts that often arise in multi-parameter space. The model provides a posterior probability of specificity for each cell subset and each sample, which can be used to profile a subject's immune response to external stimuli such as infection or vaccination.