Evidence for the expression of HLA-C class I mRNA and protein by human first trimester trophoblast

King, Ashley; Boocock, C. A.; Sharkey, Andrew; Gardner, Lucy; Beretta, Alberto; Siccardi, Antonio G.; Wai, Loke Yung

doi:10.1016/0165-0378(96)87783-7

Cited by 90 publications

(101 citation statements)

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“…The trophoblastic cells in human placenta lack classical HLA class I and class II antigens, with the exception of the expression of HLA-C during the first trimester (1,2). Although this condition prevents allorecognition and lysis by maternal T lymphocytes, it poses the problem of how trophoblastic cells can escape lysis mediated by natural killer (NK) cells.…”

mentioning

confidence: 99%

Inhibitory receptors sensing HLA-G1 molecules in pregnancy: Decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor

Ponte

Cantoni

Biassoni

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

341

247

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Trophoblastic cells lack classical HLA class I and class II molecules but express HLA-G1. Although this may prevent allorecognition by maternal T cells, it renders trophoblastic cells potentially susceptible to lysis by natural killer (NK) cells. As shown here, only a fraction of peripheralblood NK cells in pregnant women express the HLA-G1-specific CD94͞NKG2A and͞or LIR-1 receptors. However, all NK cells isolated from maternal decidua during the first trimester expressed either one or both of these receptors. Perhaps more importantly, a fraction of cells expressed p49, an HLA-G1-specific inhibitory receptor, undetectable in peripheral-blood NK cells. p49 was expressed on virtually all NK cells isolated from placenta at term. Functional analyses revealed that the HLA class I-negative 221 lymphoblastoid cell line transfected with HLA-G1 was only partially protected from lysis by peripheral-blood NK cells isolated from pregnant women, whereas it was fully protected from decidual NK cells. As indicated by the addition of specific antibodies to cytolytic tests, all the above receptors contributed to HLA-G1 recognition by decidual NK cells, although p49 would appear to play a predominant role.

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mentioning

confidence: 99%

Inhibitory receptors sensing HLA-G1 molecules in pregnancy: Decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor

Ponte

Cantoni

Biassoni

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

341

247

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“…However, a complete lack of class I MHC molecules on EVT cells would render these cells susceptible to attack by maternal NK cells, a phenomenon known as the missing self (2). It has now become evident that trophoblast cells do express the nonclassical class I MHC molecules HLA-G (3, 4), HLA-E (5), as well as the classical class I MHC molecule HLA-C, which is expressed mainly during the first trimester (6,7).…”

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confidence: 99%

Complexes of HLA-G Protein on the Cell Surface Are Important for Leukocyte Ig-Like Receptor-1 Function

Gonen‐Gross¹,

Achdout²,

Gazit³

et al. 2003

The Journal of Immunology

131

134

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The nonclassical class I MHC molecule HLA-G is selectively expressed on extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. HLA-G can inhibit the killing mediated by NK cells via interaction with the inhibitory NK cell receptor, leukocyte Ig-like receptor-1 (LIR-1). Comparison of the sequence of the HLA-G molecule to other class I MHC proteins revealed two unique cysteine residues located in positions 42 and 147. Mutating these cysteine residues resulted in a dramatic decrease in LIR-1 Ig binding. Accordingly, the mutated HLA-G transfectants were less effective in the inhibition of NK killing and RBL/LIR-1 induced serotonin release. Immunoprecipitation experiments demonstrated the involvement of the cysteine residues in the formation of HLA-G protein oligomers on the cell surface. The cysteine residue located at position 42 is shown to be critical for the expression of such complexes. These oligomers, unique among the class I MHC proteins, probably bind to LIR-1 with increased avidity, resulting in an enhanced inhibitory function of LIR-1 and an impaired killing function of NK cells.

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“…If the MEM and 3D12 mAbs are widely HLA-A, -B, -C cross-reactive, coexpression with HLA-C may be particularly misleading. Besides being prone to unfolding, HLA-C is the only classical HLA class I molecule expressed in the cytotrophoblast [16]. Thus, expression of HLA-E at the fetal-maternal interface and in human tumors originating from HLA-E-negative normal counterparts [17], as well as association with tumor prognosis ([12, 18] and reviewed therein) may all be questionable.…”

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confidence: 99%

Monoclonal antibodies to HLA‐E bind epitopes carried by unfolded β₂m‐free heavy chains

Tremante¹,

Monaco²,

Ingegnere³

et al. 2015

Eur J Immunol

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Since HLA-E heavy chains accumulate free of their light β 2 -microglobulin (β 2 m) subunit, raising mAbs to folded HLA-E heterodimers has been difficult, and mAb characterization has been controversial. Herein, mAb W6/32 and 5 HLA-E-restricted mAbs (MEM-E/02, MEM-E/07, MEM-E/08, DT9, and 3D12) were tested on denatured, acid-treated, and natively folded (both β 2 m-associated and β 2 m-free) HLA-E molecules. Four distinct conformations were detected, including unusual, partially folded (and yet β 2 m-free) heavy chains reactive with mAb DT9. In contrast with previous studies, epitope mapping and substitution scan on thousands of overlapping peptides printed on microchips revealed that mAbs MEM-E/02, MEM-E/07, and MEM-E/08 bind three distinct α1 and α2 domain epitopes. All three epitopes are linear since they span just 4-6 residues and are "hidden" in folded HLA-E heterodimers. They contain at least one HLA-E-specific residue that cannot be replaced by single substitutions with polymorphic HLA-A, HLA-B, HLA-C, HLA-F, and HLA-G residues. Finally, also the MEM-E/02 and 3D12 epitopes are spatially distinct. In summary, HLA-E-specific residues are dominantly immunogenic, but only when heavy chains are locally unfolded. Consequently, the available mAbs fail to selectively bind conformed HLA-E heterodimers, and HLA-E expression may have been inaccurately assessed in some previous oncology, reproductive immunology, virology, and transplantation studies.Keywords: Conformation r HLA-E r HLA-A r -B r -C r mAbs r β 2 -microglobulin (β 2 m) Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionBeing the ligand of both the conserved CD94/NKG2A immune receptor and the variable TCR, the oligomorphic HLA-E molecule bridges classical and nonclassical HLA class I antigens [1]. Often classified among the latter, HLA-E may rather be considered an inbetweener. This definition also applies to HLA-C, since this is the least polymorphic among classical (HLA-A, -B, -C) Correspondence: Dr. Patrizio Giacomini e-mail: giacomini@ifo.it class I antigens, and shares with HLA-E several unorthodox properties, such as selective peptide binding, poor association with β 2 m [2-4], and massive accumulation in a β 2 m-free form [5,6].Although often unappreciated, unfolded and β 2 m-free heavy chains may share epitopes with fully folded HLA class I heterodimers. These "intermediate" folds may confound the assignment of antibody specificity. For instance, a mAb called Q1/28 binds HLA-B but not HLA-C when heavy chains are β 2 massociated, and HLA-C but not HLA-B when heavy chains are β 2 m-free [7]. Likewise, mAbs MEM-E/07 and MEM-E/08 bind β 2 m-free HLA-E, but cross-react with HLA-A, -B, -C heavy chainswww.eji-journal.eu Eur. J. Immunol. 2015. 45: 2356-2364 Molecular immunology 2357 associated with β 2 m [6]. Therefore, mAbs to inbetweeners require thorough characterization, including their systematic testing on both the β 2 m-associated and the β 2 m-free heavy chains specified by ...

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Evidence for the expression of HLA-C class I mRNA and protein by human first trimester trophoblast

Cited by 90 publications

References 0 publications

Inhibitory receptors sensing HLA-G1 molecules in pregnancy: Decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor

Inhibitory receptors sensing HLA-G1 molecules in pregnancy: Decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor

Complexes of HLA-G Protein on the Cell Surface Are Important for Leukocyte Ig-Like Receptor-1 Function

Monoclonal antibodies to HLA‐E bind epitopes carried by unfolded β₂m‐free heavy chains

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Evidence for the expression of HLA-C class I mRNA and protein by human first trimester trophoblast

Cited by 90 publications

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Inhibitory receptors sensing HLA-G1 molecules in pregnancy: Decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor

Inhibitory receptors sensing HLA-G1 molecules in pregnancy: Decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor

Complexes of HLA-G Protein on the Cell Surface Are Important for Leukocyte Ig-Like Receptor-1 Function

Monoclonal antibodies to HLA‐E bind epitopes carried by unfolded β2m‐free heavy chains

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Monoclonal antibodies to HLA‐E bind epitopes carried by unfolded β₂m‐free heavy chains