Peptide-Major Histocompatibility Complex Dimensions Control Proximal Kinase-Phosphatase Balance during

Tcell antigen recognition requires binding of theT cell recep-tor (TCR) to a complex between peptide antigen and major histocompatibility complex molecules (pMHC), and this recog-nition occurs at the interface between theT cell and the antigen-presenting cell. The TCR and pMHC molecules are small com-pared with other abundant cell surface molecules, and it has been suggested that small size is functionally important. We show here that elongation of bothmouse and humanMHC class I molecules abrogates T cell antigen recognition asmeasured by cytokine production and target cell killing. This elongation dis-rupted tyrosine phosphorylation and Zap70 recruitment at the contact region without affecting TCR or coreceptor binding. Contact areas with elongated forms of pMHC showed an increase in intermembrane distance and less efficient segrega-tion of CD3 from the large tyrosine phosphatase CD45. Thes