Publication Date:
2013-03-21
Description:
To assure efficient MHC class I (MHC-I) peptide loading the peptide loading complex (PLC) recruits the peptide-receptive form of MHC-I. In this process, tapasin connects MHC-I with the peptide transporter TAP and forms a stable disulfide bond with ERp57. Here, we describe an alternatively spliced tapasin transcript lacking exon 3, observed in cells infected with human cytomegalovirus. Recognition of exon 3 was regulated via G-runs, suggesting that members of the hnRNP (heterogeneous nuclear ribonucleoprotein)-family regulate expression of the ΔExon3 variant of tapasin. Exon 3 includes Cys-95, which is responsible for the disulfide bond formation with ERp57 and, consequently, interaction of the ΔExon3 variant with ERp57 was strongly impaired. Although the ΔExon3 variant specifically stabilized TAP expression but not MHC-I in tapasin-deficient cells, in tapasin-proficient cells, the ΔExon3 tapasin reduced cell surface expression of the tapasin-dependent HLA-B*44:02 allele; the stability of the tapasin-independent HLA-B*44:05 was not affected. Most importantly, detailed analysis of the PLC revealed a simultaneous binding of the ΔExon3 variant and tapasin to TAP, suggesting modification of PLC functions. Indeed, an altered MHC-I ligandome was observed in HeLa cells overexpressing the ΔExon3 variant, highlighting the potential of the alternatively spliced tapasin variant to impact CD8+ T-cell responses.
Print ISSN:
0014-2980
Electronic ISSN:
1521-4141
Topics:
Medicine
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