The Unresolved Molecular Bases of Major Histocompatibility Complex (MHC) Function with Transplantation and Diseases Linkage
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: 30 December 2025
Special Issue Editor
Interests: immunodeficiencies; autoimmune; inmunoquimica; immunogenetic
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
MHC is a group of genes that encode proteins responsible for the regulation of the immune response. The MHC function of presenting microbial and other peptides to immune-competent cells to start an immune response was mostly discovered with mouse experiments. Most relevant to clinical practice, human MHC (HLA) linkage to disease and transplantation outcomes is still not fully understood regarding their molecular bases. Only hypotheses are available to explain HLA and the particular autoimmune disease statistical association to certain HLA alleles or groups of alleles. These explanations for such associations are highly speculative, mainly used in vitro experiments, and the therapies for these diseases have been somewhat stuck over the years. The molecular physiopathology of HLA and transplantation outcomes and disease linkage needs to be discovered, and research in these fields is urgent since, for example, the statistical linkage of MHC and disease was already discovered more than 50 years ago, and many of the autoimmune-linked diseases are still treated like in the early years with scarce success. Indeed, the role of MHC/HLA extends beyond transplantation into the pathogenesis of numerous immune-mediated diseases.
In addition, there are other puzzling facts regarding MHC (and HLA): In nature, many vertebrates show a very low polymorphism in contrast to humans and laboratory mice, with both having a very high polymorphism. MHC in vertebrates living in nature must be studied to uncover more MHC functions. There are puzzling indications that transplants between spouses have good outcomes regardless of HLA compatibility. This effect must be studied in depth. On the other hand, many drugs have side effects that depend on the existence of certain HLA alleles. Finally, immune modulatory HLA and MHC genes (G, E, and F loci) are now being studied in relation to cancer, autoimmune diseases, and other diseases. This is due to the fact that in autoimmune conditions, like type 1 diabetes, MHC molecules present self-antigens that activate autoreactive T cells, and also tumor cells may downregulate MHC expression as an immune evasion strategy, making them invisible to cytotoxic T cells.
The simple explanation that MHC function presents a peptide to begin adaptive immune response does not explain the molecular bases of some of the MHC- and HLA-linked pathology. In the present Special Issue, we aim to gather research addressing all these points, not only including human and animal (i.e., bird/mouse) pathology but also including phylogeny comparisons between the MHC and evolution of different animals.
Guest Editor
Dr. Antonio Arnaiz-Villena
Prof. Dr. Antonio Arnaiz-Villena
Guest Editor
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Keywords
- HLA
- disease
- autoimmunity
- immune deficiency
- MHC phylogeny
- HLA pharmacogenomics
- immune modulatory MHC and HLA genes (G, E, F)
- transplantation
- hemochromatosis
- MHC/HLA epithelial interaction
- MHC evolu-tion
- MHC phylogenetics
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