The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection

Логунова, Н. Н.; Kapina, Marina A.; Kondratieva, Elena; Apt, Alexander S.

doi:10.3389/fimmu.2023.1183614

Cited by 3 publications

(1 citation statement)

References 52 publications

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“…e, S1). These genes have previously been shown to play crucial roles in the MHC II pathway, contributing to the antigen presentation process essential for adaptive immune responses (Accolla et al, 2019; Cloutier et al, 2021; Logunova et al, 2023). In particular, H2-Eb2 facilitates the presentation of peptides to CD4 + T-cells, while Cd74 aids in stabilizing and directing newly synthesized MHC II molecules.…”

Section: Resultsmentioning

confidence: 99%

Glia-Mediated Antigen Presentation In The Retina During Degeneration

Intonti,

Kokona,

Zinkernagel

et al. 2024

Preprint

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Glia antigen-presenting cells (APCs) are pivotal regulators of immune surveillance within the retina, maintaining tissue homeostasis and promptly responding to insults. The intricate mechanisms underlying their local coordination and activation remain unclear. Our study integrates an animal model of retinal injury, retrospective analysis of human retinas, and in vitro experiments to elucidate insights into the pivotal role of antigen presentation in neuroimmunology during retinal degeneration, uncovering the involvement of various glial cells, notably Muller glia, and microglia. Glial cells act as sentinels, detecting antigens released during degeneration and interacting with T-cells via MHC molecules, which are essential for immune responses. Microglia function as APCs via the MHC class II pathway, upregulating key molecules such as Csf1r and cytokines. In contrast, Muller cells act as atypical APCs through the MHC class I pathway, exhibiting upregulated antigen processing genes and promoting a CD8+ T-cell response. Human retinal specimens corroborate these findings, demonstrating glial activation and MHC expression correlating with degenerative changes. In vitro assays also confirmed differential T-cell migration responses to activated microglia and Muller cells, highlighting their role in shaping the immune milieu within the retina. These insights emphasize the complex interplay between glial cells and T-cells, influencing the inflammatory environment and potentially modulating degenerative processes. In summary, our study emphasizes the involvement of retinal glial cells in modulating the immune response after insults to the retinal parenchyma. Thus, unraveling the intricacies of glia-mediated antigen presentation in retinal degeneration is essential for developing precise therapeutic interventions for retinal pathologies.

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Section: Resultsmentioning

confidence: 99%

Glia-Mediated Antigen Presentation In The Retina During Degeneration

Intonti,

Kokona,

Zinkernagel

et al. 2024

Preprint

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Inability of the BCG vaccine to protect mice of the H2f haplotype at advanced stages of TB infection is associated with defective CD4+ T-cell activation in spleen

Korotetskaya,

Baikuzina,

Apt

2023

Tuberculosis

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Polygenic TB control and the sequence of innate/adaptive immune responses to infection: MHC‐II alleles determine the size of the S100A8/9‐producing neutrophil population

Logunova,

Kapina,

Dyatlov

et al. 2024

Immunology

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Among several quantitative trait loci involved in tuberculosis (TB) control in mice, one was mapped within the chromosome 17 segment occupied by the H2 complex and another within the chromosome 3 segment comprising the S100A8/9 genes, which encode neutrophil inflammatory factor S100A8/9. Previously, we developed a panel of H2‐congenic mouse strains differing by small segments of the major histocompatibility complex Class II (MHC‐II) region from TB‐susceptible H2j mice transferred onto the genetic background of the TB‐resistant C57BL/6 (H2b) strain. Susceptible B6.I‐9.3 mice differ from B6 progenitors by the alleles of their only classical MHC‐II H2‐Aβ gene. The goals of the present study were to: (i) comprehensively characterise the differences in TB‐related phenotypes between mice of the two strains and (ii) decipher interactions between the H2‐Aβ and S100A8/9 genes. Here, we describe the dynamics of TB‐related phenotypes differentiating B6.I‐9.3 and B6 mice (colony forming units counts, histopathology, lung immune cell infiltration and cytokine profiles). We show that disproportionally diminished CD4+ T‐cell population, an enlarged S100A8/9‐positive neutrophil population and higher S100A8/9 serum levels in B6.I‐9.3 mice collectively form the ‘susceptible’ phenotype before infection. An increase in IL‐17 and a decrease in intrferon‐gamma production by CD4+ T‐cells in these mice provide a mechanistic explanation of this phenotype. Using F2 segregation analysis, we show that the number of S100A8/9‐producing neutrophils in lungs and spleens and the proportion of Th17 CD4+ T‐cells in lungs are significantly lower in the presence of the MHC‐II dominant ‘resistant’ b allele compared to the recessive ‘susceptible’ j/j genotype. This provides direct genetic evidence that MHC‐II‐regulated CD4+ T‐cell landscapes determine neutrophil abundance before infection, an important pathogenic factor in TB immunity.

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The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection

Cited by 3 publications

References 52 publications

Glia-Mediated Antigen Presentation In The Retina During Degeneration

Glia-Mediated Antigen Presentation In The Retina During Degeneration

Inability of the BCG vaccine to protect mice of the H2f haplotype at advanced stages of TB infection is associated with defective CD4+ T-cell activation in spleen

Polygenic TB control and the sequence of innate/adaptive immune responses to infection: MHC‐II alleles determine the size of the S100A8/9‐producing neutrophil population

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