Homotypic and heterotypic in cis associations of MHC class I molecules at the cell surface

Ruggiero, Fernando M.; Springer, Sebastian

doi:10.1016/j.crimmu.2022.05.001

Cited by 2 publications

(2 citation statements)

References 172 publications

(281 reference statements)

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“…In this study, we have demonstrated for the first time that Atlantic cod MHC I variants travel to the endolysosomal system in an Atlantic cod cell-line system and that this is independent of cytosolic sorting signals. This is intriguing as MHC I is known to primarily localize to the plasma membrane in mammals ( Donaldson and Williams, 2009 ; Fritzsche and Springer, 2013 ; Ruggiero and Springer, 2022 ). Considering the large variability in amino acid composition and length of the cytosolic domain of the selected Atlantic cod MHC I variants ( Figure 1A ), it was surprising to observe that they all sorted to acidic compartments in ACL cells.…”

Section: Discussionmentioning

confidence: 99%

Atlantic cod (Gadus morhua) MHC I localizes to endolysosomal compartments independently of cytosolic sorting signals

Bjørnestad

Solbakken

Jakobsen

et al. 2023

Front. Cell Dev. Biol.

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Major histocompatibility complex (MHC) class I and II are crucial for the adaptive immune system because they are involved in peptide presentation to T cells. Until recently, it was believed that MHC genes and their associated immune components had been conserved since their evolutionary emergence in jawed fish. However, sequencing of the Atlantic cod (Gadus morhua) genome revealed a loss of MHC class II genes, and an extreme expansion of MHC class I genes. These findings lead to the hypothesis that a loss of the MHC class II pathway coincided with a more versatile use of MHC class I, but so far there is no direct experimental evidence in support of this. To gain a deeper understanding of the function of the expanded MHC class I, we selected five MHC class I gene variants representing five of the six clades identified in previous studies and investigated their intracellular localization in human and Atlantic cod larval cells. Intriguingly, we uncovered that all selected MHC class I variants localize to endolysosomal compartments in Atlantic cod cells. Additionally, by introducing point mutations or deletions in the cytosolic tail, we found that hypothetical sorting signals in the MHC class I cytosolic tail do not influence MHC class I trafficking. Moreover, we demonstrated that in Atlantic cod, tapasin and MHC class I colocalize on endolysosomes suggesting that peptide-loading assistance and stabilization of MHC class I occurs outside the endoplasmic reticulum. Altogether, our results demonstrate that MHC class I from Atlantic cod is sorted to the endolysosomal system, which may indicate that it interacts with exogenous peptides for potential cross presentation.

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Section: Discussionmentioning

confidence: 99%

Atlantic cod (Gadus morhua) MHC I localizes to endolysosomal compartments independently of cytosolic sorting signals

Bjørnestad

Solbakken

Jakobsen

et al. 2023

Front. Cell Dev. Biol.

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“…The cell surface distribution of membrane proteins can be studied by Förster resonance energy transfer (FRET) at the single-cell level, and a nonrandom distribution pattern of MHC class I molecules was observed over a distance range of 2-10 nm [17][18][19][20][21][22]. A second, nonrandom, and larger-scale topological organization of the MHC class I antigens was detected by indirect immunogold labeling and imaging by transmission electron microscopy (TEM) [23].…”

mentioning

confidence: 99%

HLA DQ protein changes the cell surface distribution pattern of HLA proteins as monitored by Förster resonance energy transfer and high‐resolution electron microscopy

Kormos,

Veres,

Imre

et al. 2023

Cytometry Pt A

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Peptide presentation by MHC class I and MHC class II molecules plays important roles in the regulation of the immune response. One factor in these displays is the density of antigen, which must exceed a critical threshold for the effective activation of T cells. Nonrandom distribution of MHC class I and class II has already been detected at the nanometer level and at higher hierarchical levels. It is not clear how the absence and reappearance of some protein molecules can influence the nonrandom distribution. Therefore, we performed experiments on HLA II‐deficient bare lymphocyte syndrome (BLS1) cells: we created a stable transfected cell line, tDQ6‐BLS‐1, and were able to detect the effect of the appearance of HLA‐DQ6 molecules on the homo and heteroassociation of different cell surface molecules by comparing Förster resonance energy transfer (FRET) efficiency on transfected cells to that on nontransfected BLS‐1 and JY human B‐cell lines. Our FRET results show a decrease in homoassociation FRET between HLA I chains in HLA‐DQ6‐transfected tDQ6‐BLS‐1 cells compared with the parent BLS‐1 cell line and an increase in heteroassociation FRET between HLA I and HLA II (compared with JY cells), suggesting a similar pattern of antigen presentation by the HLA‐DQ6 allele. Transmission electron microscopy (TEM) revealed that both HLA class I and class II molecules formed clusters at higher hierarchical levels on the tDQ6‐BLS‐1 cells, and the de novo synthesized HLA DQ molecules did not intersperse with HLA class I islands. These observations could be important in understanding the fine tuning of the immune response.

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Homotypic and heterotypic in cis associations of MHC class I molecules at the cell surface

Cited by 2 publications

References 172 publications

Atlantic cod (Gadus morhua) MHC I localizes to endolysosomal compartments independently of cytosolic sorting signals

Atlantic cod (Gadus morhua) MHC I localizes to endolysosomal compartments independently of cytosolic sorting signals

HLA DQ protein changes the cell surface distribution pattern of HLA proteins as monitored by Förster resonance energy transfer and high‐resolution electron microscopy

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