Activation-induced surface proteins in the identification of antigen-responsive CD4 T cells

Identification of antigen specificity of CD4 T cells is instrumental in understanding adaptive immune responses in health and disease. The high diversity of CD4 T cell repertoire combined with the functional heterogeneity of the compartment poses a challenge to the assessment of CD4 T cell responses. In spite of that, multiple technologies allow direct or indirect interrogation of antigen specificity of CD4 T cells. In the last decade, multiple surface proteins have been established as cytokine-independent surrogates of in vitro CD4 T cell activation, and have found applications in the live identification and isolation of antigen-responsive CD4 T cells. Here we review the current knowledge of the surface proteins that permit identification of viable antigen-responsive CD4 T cells with high specificity, including those capable of identifying specialized CD4 T subsets such as germinal center follicular helper T cells and CD4 regulatory T cells.