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April 6, 2021 //---The presentation of histocompatibility complex I (MHC-I) relies on the transfer of peptides from the cytoplasm to the endoplasmic reticulum, and this process is mediated by the TAP transporter.
During viral infection, the virus affects the presentation of MHC-I to CD8 T cells by blocking the activity of TAP.
Previous studies have shown that the activation of virus-specific CD8 T cells depends on the degree of crossover of dendritic cells whose TAP activity is not affected.
In a study recently published in the journal Nature Immunology, Professor J.
Magarian Blander from Weill Cornell School of Medicine and others found that the activation of protective CD8 T cells can complete TAP in cells related to the hematopoietic system.
Successfully completed in case of inactivation.
The inactivation of TAP will inhibit the circulation of MHC-1 molecules in the endosome, which in turn affects TLR-mediated cross-presentation.
However, MHC-1 molecules can accumulate in the endoplasmic reticulum-Golgi intermediate complex (ERGIC), thereby escaping the influence of the TLR signal, and then can mediate membrane vesicle transport through interaction with ER-SNARE-Sec22b, thereby completing Cross-submission process.
During viral infection, the virus affects the presentation of MHC-I to CD8 T cells by blocking the activity of TAP.
Previous studies have shown that the activation of virus-specific CD8 T cells depends on the degree of crossover of dendritic cells whose TAP activity is not affected.
In a study recently published in the journal Nature Immunology, Professor J.
Magarian Blander from Weill Cornell School of Medicine and others found that the activation of protective CD8 T cells can complete TAP in cells related to the hematopoietic system.
Successfully completed in case of inactivation.
The inactivation of TAP will inhibit the circulation of MHC-1 molecules in the endosome, which in turn affects TLR-mediated cross-presentation.
However, MHC-1 molecules can accumulate in the endoplasmic reticulum-Golgi intermediate complex (ERGIC), thereby escaping the influence of the TLR signal, and then can mediate membrane vesicle transport through interaction with ER-SNARE-Sec22b, thereby completing Cross-submission process.
(Image source: www.
nature.
com)
nature.
com)
First, the authors observed the effect of TAP deficiency on dendritic cells.
By isolating dendritic cells from TAP-deficient mice, and using AF6-88.
5 antibody to label the mature MHC-I-antigen complex, the intracellular localization of MHC-1 was analyzed.
The results show that the distribution of MHC-1 in wild-type dendritic cells is relatively scattered; while in TAP-deficient dendritic cells, MHC-I is mainly concentrated in ERGIC, and there is a strong correlation with VAMP-3 and Rab11a Sex.
By isolating dendritic cells from TAP-deficient mice, and using AF6-88.
5 antibody to label the mature MHC-I-antigen complex, the intracellular localization of MHC-1 was analyzed.
The results show that the distribution of MHC-1 in wild-type dendritic cells is relatively scattered; while in TAP-deficient dendritic cells, MHC-I is mainly concentrated in ERGIC, and there is a strong correlation with VAMP-3 and Rab11a Sex.
(Figure 1, TAP defect affects the subcellular localization of MHC-I)
After that, the author established an in vitro dendritic cell infection model of HCMV to test the influence of virus infection on the intracellular localization of MHC-1.
The authors found that in the absence of infection, a large number of intracellular MUC-I molecules co-localized with Rab11a and ERGIC-53 molecules.
In addition, the co-localization between MHC-1 and the transporter also indicates that it has the ability to recover through the endoplasmic reticulum complex instead of the Golgi apparatus.
However, after HCMV infection, MHC-I no longer co-localized with Rab11a, but co-localized with calreticulin, implying its presence in ERGIC.
In summary, these results indicate that the intracellular localization of MHC-I has changed when TAP is defective or inactivated by viral infection.
Furthermore, the author hopes to know whether the changes in the positioning of MHC-I will affect cross-presentation.
The test results show that TAP deficiency does not affect the cross-presentation ability of DC cells after phagocytosis of E.
coli-OVA, although the intracellular localization of MHC-I changes significantly when TAP is defective.
This result is consistent with previous research results.
The authors found that in the absence of infection, a large number of intracellular MUC-I molecules co-localized with Rab11a and ERGIC-53 molecules.
In addition, the co-localization between MHC-1 and the transporter also indicates that it has the ability to recover through the endoplasmic reticulum complex instead of the Golgi apparatus.
However, after HCMV infection, MHC-I no longer co-localized with Rab11a, but co-localized with calreticulin, implying its presence in ERGIC.
In summary, these results indicate that the intracellular localization of MHC-I has changed when TAP is defective or inactivated by viral infection.
Furthermore, the author hopes to know whether the changes in the positioning of MHC-I will affect cross-presentation.
The test results show that TAP deficiency does not affect the cross-presentation ability of DC cells after phagocytosis of E.
coli-OVA, although the intracellular localization of MHC-I changes significantly when TAP is defective.
This result is consistent with previous research results.
(Figure 2, TAP defect does not affect the cross-presentation of dendritic cells)
On this basis, the authors found that under the condition of defective TAP function, ERGIC played a role in mediating the transport of MHC-I intracellular membrane vesicles, and this process was no longer affected by TLR signals.
Correspondingly, the authors found that the atypical cross-presentation process depends on the regulation of Rab22a.
Correspondingly, the authors found that the atypical cross-presentation process depends on the regulation of Rab22a.
In the end, the author found through in vivo infection experiments: Even in the case of TAP deficiency, influenza virus infection can still trigger a powerful protective CD8 T cell immune response.
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
Original source: Barbet, G.
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
After that, the author established an in vitro dendritic cell infection model of HCMV to test the influence of virus infection on the intracellular localization of MHC-1.
The authors found that in the absence of infection, a large number of intracellular MUC-I molecules co-localized with Rab11a and ERGIC-53 molecules.
In addition, the co-localization between MHC-1 and the transporter also indicates that it has the ability to recover through the endoplasmic reticulum complex instead of the Golgi apparatus.
However, after HCMV infection, MHC-I no longer co-localized with Rab11a, but co-localized with calreticulin, implying its presence in ERGIC.
In summary, these results indicate that the intracellular localization of MHC-I has changed when TAP is defective or inactivated by viral infection.
Furthermore, the author hopes to know whether the changes in the positioning of MHC-I will affect cross-presentation.
The test results show that TAP deficiency does not affect the cross-presentation ability of DC cells after phagocytosis of E.
coli-OVA, although the intracellular localization of MHC-I changes significantly when TAP is defective.
This result is consistent with previous research results.
The authors found that in the absence of infection, a large number of intracellular MUC-I molecules co-localized with Rab11a and ERGIC-53 molecules.
In addition, the co-localization between MHC-1 and the transporter also indicates that it has the ability to recover through the endoplasmic reticulum complex instead of the Golgi apparatus.
However, after HCMV infection, MHC-I no longer co-localized with Rab11a, but co-localized with calreticulin, implying its presence in ERGIC.
In summary, these results indicate that the intracellular localization of MHC-I has changed when TAP is defective or inactivated by viral infection.
Furthermore, the author hopes to know whether the changes in the positioning of MHC-I will affect cross-presentation.
The test results show that TAP deficiency does not affect the cross-presentation ability of DC cells after phagocytosis of E.
coli-OVA, although the intracellular localization of MHC-I changes significantly when TAP is defective.
This result is consistent with previous research results.
(Figure 2, TAP defect does not affect the cross-presentation of dendritic cells)
On this basis, the authors found that under the condition of defective TAP function, ERGIC played a role in mediating the transport of MHC-I intracellular membrane vesicles, and this process was no longer affected by TLR signals.
Correspondingly, the authors found that the atypical cross-presentation process depends on the regulation of Rab22a.
Correspondingly, the authors found that the atypical cross-presentation process depends on the regulation of Rab22a.
In the end, the author found through in vivo infection experiments: Even in the case of TAP deficiency, influenza virus infection can still trigger a powerful protective CD8 T cell immune response.
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
Original source: Barbet, G.
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
On this basis, the authors found that under the condition of defective TAP function, ERGIC played a role in mediating the transport of MHC-I intracellular membrane vesicles, and this process was no longer affected by TLR signals.
Correspondingly, the authors found that the atypical cross-presentation process depends on the regulation of Rab22a.
Correspondingly, the authors found that the atypical cross-presentation process depends on the regulation of Rab22a.
In the end, the author found through in vivo infection experiments: Even in the case of TAP deficiency, influenza virus infection can still trigger a powerful protective CD8 T cell immune response.
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
Original source: Barbet, G.
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
In the end, the author found through in vivo infection experiments: Even in the case of TAP deficiency, influenza virus infection can still trigger a powerful protective CD8 T cell immune response.
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
Original source: Barbet, G.
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
In the end, the author found through in vivo infection experiments: Even in the case of TAP deficiency, influenza virus infection can still trigger a powerful protective CD8 T cell immune response.
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
The survival and weight loss trends of mice were not significantly different from those of wild-type mice.
In summary, the author revealed a new type of cross-presentation mechanism that does not rely on TAP protein through cell biology and immunological methods.
(Bioon.
com)
Original source: Barbet, G.
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
Original source: Barbet, G.
, Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
Original source: TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming. , Nair-Gupta, P.
, Schotsaert, M.
et al.
TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.
Nat Immunol 22, 497–509 (2021).
https: //doi.
org/10.
1038/s41590-021-00903-7
Nat Immunol 22,
