Major Histocompatibility Complex (MHC) and Fungal Antigen Presentation: Immunological Mechanisms and Their Role in Anti-Fungal Immunity
9 affiliations
- 1Department of Anatomy, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise 533000, China
- 2Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand
- 3Department of Medical Science, Mahidol University Amnatcharoen Campus, Amnatcharoen 37000, Thailand
- 4Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- 5Covenant HealthCare College of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USA
- 6Department of Food Industry, School of Agricultural Technology and Food Industry, Walailak University, Nakhon Si Thammarat 80160, Thailand
- 7School of Medical Imaging, Youjiang Medical University for Nationalities, Baise 533000, China
- 8Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand
- 9Research Center for Microbiome, Systems Biology and Medical Innovation (MiSys Center), Walailak University, Nakhon Si Thammarat 80160, Thailand
Abstract
Cellular-mediated immunity against invasive fungal infections is fundamentally governed by Major Histocompatibility Complex (MHC) restriction, whereby T cells detect fungal invasion indirectly through peptide fragments displayed on host MHC molecules rather than by recognizing intact fungal pathogens. In contrast to B cells, which bind native microbial antigens, T lymphocytes monitor antigen-presenting cells for processed fungal peptides presented by MHC class I and class II molecules. This review examines the molecular mechanisms underlying fungal antigen processing and presentation, emphasizing the pivotal contributions of MHC class II-restricted CD4 T-helper (TH1/TH17) cells and cross-presented, MHC class I-restricted CD8 cytotoxic T lymphocytes to antifungal host defense. We also summarize key experimental approaches, including overlapping peptide libraries, ELISpot assays, and peptide–MHC multimers, for defining MHC function and identifying immunodominant fungal antigenic determinants. Evidence from representative pathogenic fungal antigens, including Asp f16, Crf1, Eng2, and the multivalent rCpa1 vaccine, highlights both the promise and complexity of achieving cross-protective cellular immunity. Importantly, amino acid sequence similarity alone is insufficient to predict T-cell cross-reactivity, indicating that computational prediction and experimental epitope mapping should be employed as complementary approaches for the accurate identification and validation of immunologically relevant epitopes. Finally, elucidating the molecular principles governing fungal peptide presentation establishes a rational foundation for the development of broadly protective epitope-based vaccines and next-generation immunotherapeutic strategies.
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BibTeX
@article{shu2026major,
title = {{Major Histocompatibility Complex (MHC) and Fungal Antigen Presentation: Immunological Mechanisms and Their Role in Anti-Fungal Immunity}},
author = {Fangyi Shu and Nopawit Khamto and Artid Amsri and Sirida Youngchim and Joshua D. Nosanchuk and Thinnaphop Chum-in and Qingping Deng and Kritsada Pruksaphon},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219533},
url = {https://www.mdpi.com/1422-0067/27/21/9533},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Major Histocompatibility Complex (MHC) and Fungal Antigen Presentation: Immunological Mechanisms and Their Role in Anti-Fungal Immunity
AU - Fangyi Shu
AU - Nopawit Khamto
AU - Artid Amsri
AU - Sirida Youngchim
AU - Joshua D. Nosanchuk
AU - Thinnaphop Chum-in
AU - Qingping Deng
AU - Kritsada Pruksaphon
PY - 2026
DA - 2026/10/25
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219533
UR - https://www.mdpi.com/1422-0067/27/21/9533
AB - Cellular-mediated immunity against invasive fungal infections is fundamentally governed by Major Histocompatibility Complex (MHC) restriction, whereby T cells detect fungal invasion indirectly through peptide fragments displayed on host MHC molecules rather than by recognizing intact fungal pathogens. In contrast to B cells, which bind native microbial antigens, T lymphocytes monitor antigen-presenting cells for processed fungal peptides presented by MHC class I and class II molecules. This review examines the molecular mechanisms underlying fungal antigen processing and presentation, emphasizing the pivotal contributions of MHC class II-restricted CD4 T-helper (TH1/TH17) cells and cross-presented, MHC class I-restricted CD8 cytotoxic T lymphocytes to antifungal host defense. We also summarize key experimental approaches, including overlapping peptide libraries, ELISpot assays, and peptide–MHC multimers, for defining MHC function and identifying immunodominant fungal antigenic determinants. Evidence from representative pathogenic fungal antigens, including Asp f16, Crf1, Eng2, and the multivalent rCpa1 vaccine, highlights both the promise and complexity of achieving cross-protective cellular immunity. Importantly, amino acid sequence similarity alone is insufficient to predict T-cell cross-reactivity, indicating that computational prediction and experimental epitope mapping should be employed as complementary approaches for the accurate identification and validation of immunologically relevant epitopes. Finally, elucidating the molecular principles governing fungal peptide presentation establishes a rational foundation for the development of broadly protective epitope-based vaccines and next-generation immunotherapeutic strategies.
SN - 1422-0067
ER -