Ribosylation of the CD8αβ heterodimer permits binding of the nonclassical major histocompatibility molecule, H2-Q10

Goodall, Katharine J.; Nguyen, Angela; Andrews, Daniel M.; Sullivan, Lucy C.

doi:10.1016/j.jbc.2021.101141

Cited by 2 publications

(2 citation statements)

References 39 publications

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“…Indeed, CD8 expression is regulated transcriptionally ( Bosselut et al, 2003 ; Park et al, 2007 ) and by modulation at the cell surface ( Maile et al, 2005 ; Xiao et al, 2007 ). In addition, post-translational modifications of CD8αα and CD8αβ proteins can alter their ability to bind MHC-Ia molecules ( Daniels et al, 2001 ; Moody et al, 2001 ; Kao et al, 2006 ; Lischke et al, 2013 ) and MHC-Ib molecules, as recently demonstrated for H2-Q10 ( Goodall et al, 2021 ). It is also known that CD8αα can be induced on IELs, conventional T cells, and immature thymocytes in response to microenvironmental cues and TCR stimulation ( Reis et al, 2013 ; Gangadharan and Cheroutre, 2004 ).…”

Section: Discussionmentioning

confidence: 94%

CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells

Souter

Awad

et al. 2022

Journal of Experimental Medicine

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Mucosal-associated invariant T (MAIT) cells detect microbial infection via recognition of riboflavin-based antigens presented by the major histocompatibility complex class I (MHC-I)–related protein 1 (MR1). Most MAIT cells in human peripheral blood express CD8αα or CD8αβ coreceptors, and the binding site for CD8 on MHC-I molecules is relatively conserved in MR1. Yet, there is no direct evidence of CD8 interacting with MR1 or the functional consequences thereof. Similarly, the role of CD8αα in lymphocyte function remains ill-defined. Here, using newly developed MR1 tetramers, mutated at the CD8 binding site, and by determining the crystal structure of MR1–CD8αα, we show that CD8 engaged MR1, analogous to how it engages MHC-I molecules. CD8αα and CD8αβ enhanced MR1 binding and cytokine production by MAIT cells. Moreover, the CD8–MR1 interaction was critical for the recognition of folate-derived antigens by other MR1-reactive T cells. Together, our findings suggest that both CD8αα and CD8αβ act as functional coreceptors for MAIT and other MR1-reactive T cells.

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Section: Discussionmentioning

confidence: 94%

CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells

Souter

Awad

et al. 2022

Journal of Experimental Medicine

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“…For example, Pydc4 , Rhov , Oasl1 , Hdc , Isg15 , Il1f9 , Saa3 , Ccl4 , Treml2 , H2‐Q10 , and Cebpe in primary tumors and Ly6c2 , CD8b1 , Gimap5 , Lat , Hcst , Cd3d , Pglyrp1 , Tusc5 and H2‐Q10 in abscopal tumors were significantly downregulated with the absence of TDLN. Because most of these genes are associated with T cell function [ 35 , 36 , 37 , 38 ], the finding indicated that the removal of bilateral TDLN might lead to impaired iRT‐induced T cell responses.…”

Section: Resultsmentioning

confidence: 99%

Pivotal roles of tumor‐draining lymph nodes in the abscopal effects from combined immunotherapy and radiotherapy

Liu

Chen

et al. 2022

Cancer Communications

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Background Currently, due to synergy enhancement of anti‐tumor effects and potent stimulation of abscopal effects, combination therapy with irradiation and programmed cell death protein 1/programmed death‐ligand 1 (PD‐1/PD‐L1) immune checkpoint inhibition (immuno‐radiotherapy, iRT) has revolutionized the therapeutic guidelines. It has been demonstrated that tumor‐draining lymph nodes (TDLN) are essential for effective antitumor immunity induced by radiotherapy, immunotherapy, or iRT. Given that the function of TDLN in iRT remains unclear, this study aimed to investigate the function and mechanism of TDLN in iRT‐induced abscopal effects. Methods The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated TDLN. The flow cytometry, multiple immunofluorescence analysis, and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor microenvironment. Additionally, we tempted to interrogate the possible mechanisms via RNA‐sequencing of tumor‐infiltrating lymphocytes and TDLN. Results TDLN deficiency impaired the control of tumor growth by monotherapy. Bilateral TDLN removal rather than unilateral TDLN removal substantially curtailed iRT‐stimulated anti‐tumor and abscopal effects. Furthermore, in the absence of TDLN, the infiltration of CD45+ and CD8+ T cells was substantially reduced in both primary and abscopal tumors, and the anti‐tumor function of CD8+ T cells was attenuated as well. Additionally, the polarization of tumor‐associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral TDLN. RNA‐sequencing data indicated that impaired infiltration and anti‐tumor effects of immune cells partially attributed to the altered secretion of components from the tumor microenvironment. Conclusions TDLN play a critical role in iRT by promoting the infiltration of CD8+ T cells and maintaining the M1/M2 macrophage ratio.

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Ribosylation of the CD8αβ heterodimer permits binding of the nonclassical major histocompatibility molecule, H2-Q10

Cited by 2 publications

References 39 publications

CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells

CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells

Pivotal roles of tumor‐draining lymph nodes in the abscopal effects from combined immunotherapy and radiotherapy

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