CD4 and arthritic joint disease: LCK can bind to cell surface receptors (including CD4 and CD8) and other signaling molecules (Hu et al., 2022), while mutations in ZAP70 change the sensitivity of developing T cells to thymic positive/negative selection by altering self-peptide/MHC complexes, change the self-reactive TCR repertoire to include dominant arthritis-specific ones, and affect thymic development and the production of self-immune inhibitory regulatory T cells (Treg) (Takeuchi et al., 2020).