ISOFORMS OF THE TRANSMEMBRANE TYROSINE PHOSPHATASE CD45 DIFFERENTIALLY AFFECT T-CELL RECOGNITION

Activation of T cells has been shown to require CD45. CD45 is expressed on T cells as distinct isoforms and these isoforms are expressed differentially on subsets of CD4 T cells. We have generated T cell lines expressing a T cell receptor (TCR) of known specificity, with or without CD4, and examined the effect of different CD45 isoforms on stimulation through the antigen receptor. We find that isoforms differ in their ability to participate in antigen recognition, with the null isoform that is predominantly found on memory CD4 T cells being the most effective. The ability of the CD45 ectodomain to differentially affect sensitivity to specific ligands represents a novel way of regulating the efficacy of signaling through a receptor without altering its specificity. It may play a crucial role both in immunological memory and during intrathymic maturation of T cells.