HLA-DP84Gly constitutively presents endogenous peptides generated by the class I antigen processing pathway

Yuki Yamashita, Mark Anczurowski, Munehide Nakatsugawa, Makito Tanaka, Yuki Kagoya, Ankit Sinha, Kenji Chamoto, Toshiki Ochi, Tingxi Guo, Kayoko Saso, Marcus O. Butler, Mark D. Minden, Thomas Kislinger and Naoto Hirano ()
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Yuki Yamashita: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Mark Anczurowski: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Munehide Nakatsugawa: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Makito Tanaka: Dana-Farber Cancer Institute
Yuki Kagoya: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Ankit Sinha: Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Kenji Chamoto: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Toshiki Ochi: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Tingxi Guo: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Kayoko Saso: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Marcus O. Butler: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Mark D. Minden: Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network,
Thomas Kislinger: Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network
Naoto Hirano: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Classical antigen processing leads to the presentation of antigenic peptides derived from endogenous and exogenous sources for MHC class I and class II molecules, respectively. Here we show that, unlike other class II molecules, prevalent HLA-DP molecules with β-chains encoding Gly84 (DP84Gly) constitutively present endogenous peptides. DP84Gly does not bind invariant chain (Ii) via the class II-associated invariant chain peptide (CLIP) region, nor does it present CLIP. However, Ii does facilitate the transport of DP84Gly from the endoplasmic reticulum (ER) to the endosomal/lysosomal pathway by transiently binding DP84Gly via a non-CLIP region(s) in a pH-sensitive manner. Accordingly, like class I, DP84Gly constitutively presents endogenous peptides processed by the proteasome and transported to the ER by the transporter associated with antigen processing (TAP). Therefore, DP84Gly, found only in common chimpanzees and humans, uniquely uses both class I and II antigen-processing pathways to present peptides derived from intracellular and extracellular sources.

Date: 2017
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DOI: 10.1038/ncomms15244

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