PMID- 36399818
OWN - NLM
STAT- MEDLINE
DCOM- 20221206
LR  - 20230111
IS  - 1090-2163 (Electronic)
IS  - 0008-8749 (Linking)
VI  - 382
DP  - 2022 Dec
TI  - Kinetics of antigen cross-presentation assessed experimentally and by a model of 
      the complete endomembrane system.
PG  - 104636
LID - S0008-8749(22)00161-7 [pii]
LID - 10.1016/j.cellimm.2022.104636 [doi]
AB  - Dendritic cells (DCs) have a specialized endomembrane system capable of 
      presenting exogenous antigens in the context of MHC class I (MHC-I) molecules. 
      This process, named cross-presentation, is crucial to activate CD8+ T lymphocytes 
      and initiate cytotoxic immune responses. In this report, we present an 
      Agent-Based Model in combination with Ordinary Differential Equations with enough 
      complexity to reproduce cross-presentation. The model embraces the secretory and 
      endocytic pathways, in connection with the plasma membrane, the endoplasmic 
      reticulum, and the cytosol. Key molecules required for cross-presentation were 
      included as cargoes. In the simulations, the kinetics of MHC-I uptake and 
      recycling, and cross-presentation accurately reproduced experimental values. The 
      model proved to be a suitable tool to elaborate hypotheses and design 
      experiments. In particular, the model predictions and the experimental results 
      obtained indicate that the rate-limiting step in cross-presentation of soluble 
      ovalbumin is MHC-I loading after proteasomal processing of the antigenic protein.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Nieto, Franco
AU  - Nieto F
AD  - Instituto de Histologia y Embriologia de Mendoza (IHEM) - Universidad Nacional de 
      Cuyo - CONICET, Mendoza 5500, Argentina.
FAU - Garrido, Facundo
AU  - Garrido F
AD  - Instituto de Histologia y Embriologia de Mendoza (IHEM) - Universidad Nacional de 
      Cuyo - CONICET, Mendoza 5500, Argentina.
FAU - Dinamarca, Sofia
AU  - Dinamarca S
AD  - Instituto de Histologia y Embriologia de Mendoza (IHEM) - Universidad Nacional de 
      Cuyo - CONICET, Mendoza 5500, Argentina.
FAU - Cebrian, Ignacio
AU  - Cebrian I
AD  - Instituto de Histologia y Embriologia de Mendoza (IHEM) - Universidad Nacional de 
      Cuyo - CONICET, Mendoza 5500, Argentina. Electronic address: 
      icebrian@mendoza-conicet.gob.ar.
FAU - Mayorga, Luis S
AU  - Mayorga LS
AD  - Instituto de Histologia y Embriologia de Mendoza (IHEM) - Universidad Nacional de 
      Cuyo - CONICET, Mendoza 5500, Argentina; Facultad de Ciencias Exactas y 
      Naturales, Universidad Nacional de Cuyo, Mendoza 5500, Argentina. Electronic 
      address: lmayorga@mendoza-conicet.gob.ar.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221106
PL  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - *Cross-Priming
MH  - Kinetics
MH  - *Antigen Presentation
MH  - Ovalbumin
MH  - CD8-Positive T-Lymphocytes
OTO - NOTNLM
OT  - COPASI
OT  - Cross-presentation
OT  - Dendritic cells
OT  - Endocytic pathway model
OT  - Intracellular transport
OT  - MHC-I molecules
OT  - Repast
OT  - Secretory pathway model
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/11/19 06:00
MHDA- 2022/12/07 06:00
CRDT- 2022/11/18 18:14
PHST- 2022/07/01 00:00 [received]
PHST- 2022/10/18 00:00 [revised]
PHST- 2022/10/24 00:00 [accepted]
PHST- 2022/11/19 06:00 [pubmed]
PHST- 2022/12/07 06:00 [medline]
PHST- 2022/11/18 18:14 [entrez]
AID - S0008-8749(22)00161-7 [pii]
AID - 10.1016/j.cellimm.2022.104636 [doi]
PST - ppublish
SO  - Cell Immunol. 2022 Dec;382:104636. doi: 10.1016/j.cellimm.2022.104636. Epub 2022 
      Nov 6.