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CD8+ T Cells and MHC Class I Molecules at the Interface Between Biology and Biomedicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 17044

Special Issue Editors

Dr. Fernando A. Arosa

E-Mail Website
Guest Editor
Health Sciences Research Center (CICS-UBI), University of Beira Interior, Covilha, Portugal
Interests: humans; CD8+ T cells; cytokines; CD8αβ; CD8αα; CD45RA; NK receptors; open MHC-I conformers; neuroimmunology
Dr. Elsa Maria Cardoso

E-Mail Website
Guest Editor
Health Sciences Research Center (CICS-UBI), University of Beira Interior, Covilhã, Portugal
Interests: CD8+ T-cells; MHC class I; Immune Biomarkers; Neuroimmunology

Special Issue Information

Dear Colleagues,

CD8+ T cells and MHC class I molecules (MHC-I) play a central role in the “modus operandi” of the immunological system. Moreover, the scientific knowledge acquired on the biology, biochemistry, and physiology of CD8+ T cells and MHC-I molecules has always followed intertwined paths. Thus, the pool of CD8+ T cells that recirculates between blood, tissues, and lymph is heterogeneous and endowed with the capacity to sense external and internal threats. As a result, CD8+ T cells can start a diversity of responses, including cytotoxic, inflammatory, suppressor, and those related to tissue repair and regeneration. Most of these responses rely on the trans-interaction between the TCR of CD8+ T cells and MHC-I molecules expressed by dendritic cells and complexed with peptides from external and internal proteins. However, MHC-I molecules can also trans-interact with activation and inhibitory NK receptors expressed by lymphomyeloid cells, regulating their function. Finally, MHC-I molecules can also cis-interact with adjacent cell surface receptors, including inhibitory and stimulatory receptors, cytokine receptors, and hormone/growth factor receptors, with important biological and biomedical implications. Underneath the cis–trans features of MHC-I molecules and the diversity of CD8+ T cell responses lie many contemporary biomedical issues. These include, but are not limited to, deregulated cell growth (e.g., cancer) and immunological responses (e.g., autoimmunity, transplantation) as well as deficient tissue homeostasis (e.g., neurodegeneration). 

The IJMS and the Editors of this Special Issue welcome original articles, short communications, opinion articles, and reviews that focus on the biology of CD8+ T cells and MHC-I molecules and their relevance to contemporary biomedicine.

Dr. Fernando A. Arosa
Dr. Elsa Maria Cardoso
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CD8
  • MHC-I
  • open conformers
  • growth factors
  • receptors
  • cancer
  • autoimmunity
  • transplantation
  • neuroimmunology

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Published Papers (4 papers)

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Research

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18 pages, 3621 KiB  
Article
Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes
by Hernani Gil-Julio, Francisco Perea, Antonio Rodriguez-Nicolas, Jose Manuel Cozar, Amanda Rocío González-Ramirez, Angel Concha, Federico Garrido, Natalia Aptsiauri and Francisco Ruiz-Cabello
Int. J. Mol. Sci. 2021, 22(14), 7248; https://doi.org/10.3390/ijms22147248 - 6 Jul 2021
Cited by 13 | Viewed by 3317
Abstract
Cancer eradication and clinical outcome of immunotherapy depend on tumor cell immunogenicity, including HLA class I (HLA-I) and PD-L1 expression on malignant cells, and on the characteristics of the tumor microenvironment, such as tumor immune infiltration and stromal reaction. Loss of tumor HLA-I [...] Read more.
Cancer eradication and clinical outcome of immunotherapy depend on tumor cell immunogenicity, including HLA class I (HLA-I) and PD-L1 expression on malignant cells, and on the characteristics of the tumor microenvironment, such as tumor immune infiltration and stromal reaction. Loss of tumor HLA-I is a common mechanism of immune escape from cytotoxic T lymphocytes and is linked to cancer progression and resistance to immunotherapy with the inhibitors of PD-L1/PD-1 signaling. Here we observed that HLA-I loss in bladder tumors is associated with T cell exclusion and tumor encapsulation with stromal elements rich in FAP-positive cells. In addition, PD-L1 upregulation in HLA-I negative tumors demonstrated a correlation with high tumor grade and worse overall- and cancer-specific survival of the patients. These changes define common immuno-morphological signatures compatible with cancer immune escape and acquired resistance to therapeutic interventions across different types of malignancy. They also may contribute to the search of new targets for cancer treatment, such as FAP-expressing cancer-associated fibroblasts, in refractory bladder tumors. Full article
(This article belongs to the Special Issue CD8+ T Cells and MHC Class I Molecules at the Interface Between Biology and Biomedicine)
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Review

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23 pages, 2094 KiB  
Review
The HLA-G Immune Checkpoint Plays a Pivotal Role in the Regulation of Immune Response in Autoimmune Diseases
by Monika Zaborek-Łyczba, Jakub Łyczba, Paulina Mertowska, Sebastian Mertowski, Anna Hymos, Martyna Podgajna, Paulina Niedźwiedzka-Rystwej and Ewelina Grywalska
Int. J. Mol. Sci. 2021, 22(24), 13348; https://doi.org/10.3390/ijms222413348 - 12 Dec 2021
Cited by 15 | Viewed by 3403
Abstract
The human G-leukocyte antigen (HLA-G) molecule is a non-classical major histocompatibility complex (MHC) class I molecule. The pertinence of HLA-G has been investigated in numerous studies which have sought to elucidate the relevance of HLA-G in pathologic conditions, such as autoimmune diseases, cancers, [...] Read more.
The human G-leukocyte antigen (HLA-G) molecule is a non-classical major histocompatibility complex (MHC) class I molecule. The pertinence of HLA-G has been investigated in numerous studies which have sought to elucidate the relevance of HLA-G in pathologic conditions, such as autoimmune diseases, cancers, and hematologic malignancies. One of the main goals of the current research on HLA-G is to use this molecule in clinical practice, either in diagnostics or as a therapeutic target. Since HLA-G antigens are currently considered as immunomodulatory molecules that are involved in reducing inflammatory and immune responses, in this review, we decided to focus on this group of antigens as potential determinants of progression in autoimmune diseases. This article highlights what we consider as recent pivotal findings on the immunomodulatory function of HLA-G, not only to establish the role of HLA-G in the human body, but also to explain how these proteins mediate the immune response. Full article
(This article belongs to the Special Issue CD8+ T Cells and MHC Class I Molecules at the Interface Between Biology and Biomedicine)
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27 pages, 3042 KiB  
Review
Open MHC Class I Conformers: A Look through the Looking Glass
by Fernando A. Arosa, André J. Esgalhado, Débora Reste-Ferreira and Elsa M. Cardoso
Int. J. Mol. Sci. 2021, 22(18), 9738; https://doi.org/10.3390/ijms22189738 - 8 Sep 2021
Cited by 11 | Viewed by 6045
Abstract
Studies carried out during the last few decades have consistently shown that cell surface MHC class I (MHC-I) molecules are endowed with functions unrelated with antigen presentation. These include cis–trans-interactions with inhibitory and activating KIR and LILR, and cis-interactions with receptors for hormones, [...] Read more.
Studies carried out during the last few decades have consistently shown that cell surface MHC class I (MHC-I) molecules are endowed with functions unrelated with antigen presentation. These include cis–trans-interactions with inhibitory and activating KIR and LILR, and cis-interactions with receptors for hormones, growth factors, cytokines, and neurotransmitters. The mounting body of evidence indicates that these non-immunological MHC-I functions impact clinical and biomedical settings, including autoimmune responses, tumor escape, transplantation, and neuronal development. Notably, most of these functions appear to rely on the presence in hematopoietic and non-hematopoietic cells of heavy chains not associated with β2m and the peptide at the plasma membrane; these are known as open MHC-I conformers. Nowadays, open conformers are viewed as functional cis-trans structures capable of establishing physical associations with themselves, with other surface receptors, and being shed into the extracellular milieu. We review past and recent developments, strengthening the view that open conformers are multifunctional structures capable of fine-tuning cell signaling, growth, differentiation, and cell communication. Full article
(This article belongs to the Special Issue CD8+ T Cells and MHC Class I Molecules at the Interface Between Biology and Biomedicine)
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Other

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9 pages, 1272 KiB  
Opinion
What Is the Role of HLA-I on Cancer Derived Extracellular Vesicles? Defining the Challenges in Characterisation and Potential Uses of This Ligandome
by Caitlin Boyne, Debra Lennox, Olivia Beech, Simon J. Powis and Pankaj Kumar
Int. J. Mol. Sci. 2021, 22(24), 13554; https://doi.org/10.3390/ijms222413554 - 17 Dec 2021
Cited by 6 | Viewed by 3317
Abstract
The Human Leukocyte Antigen class I (HLA-I) system is an essential part of the immune system that is fundamental to the successful activation of cytotoxic lymphocytes, and an effective subsequent immune attack against both pathogen-infected and cancer cells. The importance of cytotoxic T [...] Read more.
The Human Leukocyte Antigen class I (HLA-I) system is an essential part of the immune system that is fundamental to the successful activation of cytotoxic lymphocytes, and an effective subsequent immune attack against both pathogen-infected and cancer cells. The importance of cytotoxic T cell activity and ability to detect foreign cancer-related antigenic peptides has recently been highlighted by the successful application of monoclonal antibody-based checkpoint inhibitors as novel immune therapies. Thus, there is an increased interest in fully characterising the repertoire of peptides that are being presented to cytotoxic CD8+ T cells by cancer cells. However, HLA-I is also known to be present on the surface of extracellular vesicles, which are released by most if not all cancer cells. Whilst the peptide ligandome presented by cell surface HLA class I molecules on cancer cells has been studied extensively, the ligandome of extracellular vesicles remains relatively poorly defined. Here, we will describe the current understanding of the HLA-I peptide ligandome and its role on cancer-derived extracellular vesicles, and evaluate the aspects of the system that have the potential to advance immune-based therapeutic approaches for the effective treatment of cancer. Full article
(This article belongs to the Special Issue CD8+ T Cells and MHC Class I Molecules at the Interface Between Biology and Biomedicine)
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