Regulation of transporter associated with antigen processing by phosphorylation

The ATP-binding cassette transporter associated with antigen processing (TA P) is required for transport of antigenic peptides, generated by proteasome complexes in the cytoplasm, into the lumen of the endoplasmic reticulum wh ere assembly with major histocompatibility complex class I molecules takes place. The TAP transporter is a heterodimer of TAP1 and TAPS, Here we show that both TAP1 and TAPS are phosphorylated under physiological conditions. Phosphorylation induces formation of high molecular weight TAP complexes th at contain TAP1, TAPS, tapasin, and class I heterodimers, In addition, a 43 -kDa phosphoprotein, which appears to be a kinase, is contained in the phos phorylated TAP-containing complexes. Phosphorylated TAP complexes are able to bind peptides and ATP, however, they are not capable of transporting pep tides. After de-phosphorylation, TAP complexes regain the ability to transp ort peptides, Interestingly, phosphorylation levels of TAP complexes induce d by viral infection inversely correlates with a significant reduction in T AP-dependent peptide transport activity. Enhanced TAP phosphorylation appea rs to be one of several strategies that viruses have exploited to better es cape from host immune surveillance. These results demonstrate that major hi stocompatibility complex class I antigen processing and presentation is mod ulated by reversible TAP phosphorylation, and implicate the importance of T AP phosphorylation in the regulation of cytotoxic immune response.