Determination of antigen-specific T cell repertoires in human has been a challenge. Here, we show a novel integrated approach that permits determination of multiple parameters of antigen-specific T cell repertoires. Briefly, human PBMCs are first stimulated with overlapping peptides encoding a given antigen for 48 hours to measure cytokine production (Direct assay). Peptide-reactive T cells are further expanded by IL-2 for 5 days and re-stimulated with the same peptides from the initial culture to analyze cytokine production (Cytokine-driven assay). We first applied this approach to determine the type of ZnT8-specific T cells in healthy adults. Out of ten donors, the Direct assay identified ZnT8-specific CD4+ T cells in five adults. Furthermore, these ZnT8-specific CD4+ T cells belonged to the CD45RO+ memory compartment. The Cytokine-driven assay further revealed that those specific CD4+ T cells were capable of producing various types of cytokines including type 1 and type 2 cytokines as well as IL-10. We next applied our integrated assay to determine whether the type of ZnT8-specific CD4+ T cells is different between Type 1 diabetes patients (n=15) and age/gender/HLA-matched healthy subjects (n=15). We found that ZnT8-specific CD4+ T cells were skewed towards Th1 cells in T1D patients (p=0.0001 in the percentage of IL-10-IL-13-IFN-γ+CD4+ T cells), while Th2 and IL-10-producing cells were prevalent in healthy subjects (p=0.03 and p=0.04 in the percentage of IL-10+IL-13+IFN-γ-CD4+ and IL-10+IL-13-IFN-γ-CD4+ T cells, respectively). In conclusion, the Direct assay and the Cytokine-driven assay complement each other, and the combination of the two assays provides information of antigen-specific T cell repertoires on the breadth, type, and avidity. This strategy is applicable to determine the differences in the quality of antigen-specific T cells between health and disease