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Major Histocompatibility Complex class I heavy chains localize in both cytoplasmic and nuclear compartment

Gomez-Herranz, M.; Dziadosz, A.; Mikac, S.; Rychlowski, M.; Fahraeus, R.; Marek-Trzonkowska, N.; Chrusciel, E.; Urban-Wojciuk, Z.; Papak, I.; Arcimowicz, L.; Marjanski, T.; Rzyman, W.; Sznarkowska, A.

2022-09-15 immunology
10.1101/2022.09.13.507738 bioRxiv
Show abstract

The Major Histocompatibility Complex class I (MHC-I) molecules present antigenic peptides (AP) to CD8+ T cells for self versus non-self recognition. Loading of AP on MHC-I takes place in the endoplasmic reticulum (ER), upon shuttling of cytoplasmic AP substrates to the ER. Understanding of this process has been influenced by the view that MHC-I antigens are produced from the proteasomal degradation of cellular proteins. Recent observations on the intronic and untranslated region-derived peptides as well as on the non-AUG translation products presented on the MHC-I open the possibility that antigenic peptides can derive from pre-spliced mRNAs translated in the nuclear compartment. In this brief report, we show that a fraction of human MHC-I molecules (human leukocyte antigens type A, HLA-A) is present in the nuclei of cells, in the proximity of histone H2B. With this finding, we hope to initiate a new direction of research on the nuclear role of MHC-I and ask whether the loading of antigens can take place in the nuclear compartment.

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