Induction and functional characterization of β 2-microglobulin (β2-μ)-free HLA class I heavy chains expressed by β2-μ-deficient human FO-1 melanoma cells

Wang, Zhigang; Arienti, Flavio; Parmiani, Giorgio; Ferrone, Soldano

doi:10.1002/(sici)1521-4141(199809)28:09<2817::aid-immu2817>3.0.co;2-m

Cited by 12 publications

(11 citation statements)

References 34 publications

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“…Herein, we confirm the extreme instability of Daudi heavy chains, but at the same time conclusively show that, unlike the other ␤ 2 m-deficient human cells described so far (7)(8)(9)(10)(11)(12)(13)(14), Daudi cells synthesize class I molecules with biochemical features intermediate between those of folded and unfolded heavy chains, and surface-express them at low levels. Thus, we propose amendments and refinements in the fields of class I folding as well as virus and tumor immune surveillance.…”

Section: Discussionmentioning

confidence: 98%

“…To our knowledge, class I HLA heavy chains from ␤ 2 m-deficient cells other than Daudi lack conformational epitopes (7)(8)(9)(10)(11)(12)(13)(14). To confirm this difference in a controlled experiment, we compared side-by-side Daudi cells, three ␤ 2 m-defective cell lines characterized by three different groups (KJ-29 (12), FO-1 (7), and LoVo (10)), and two stable ␤ 2 m transfectants (Fig.…”

Section: The ␤ 2 M-free Class I Heavy Chains Synthesized By Daudi Celmentioning

confidence: 99%

“…Although several human ␤ 2 m-defective human cell lines have been described, and some of them express surface free heavy chains reactive with Abs to linear epitopes (7)(8)(9)(10)(11)(12)(13)(14), no free heavy chains of human origin other than those expressed by Daudi cells were demonstrably reactive with W6/32. The question then arises of what makes Daudi cells unique.…”

Section: Implications For Tumor Immune Surveillancementioning

confidence: 99%

“…Class I heavy chains from these cells (including the first and possibly most studied ␤ 2 m mutant, the Burkitt lymphoma cell line Daudi) do not spontaneously acquire conformational epitopes (4 -14) and/or thermal stability (6,15,16), are not recruited by chaperones in the so-called peptide loading complex (17), and display poor intracellular transport (4,5). Even when surface-expressed, ␤ 2 m-free heavy chains do not properly fold or present Ag (12,14), although there is some controversy as to whether (18) or not (19) these "open conformers" might influence NK cell lysis, and possibly other functions (reviewed in Ref. 20).…”

mentioning

confidence: 99%

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Class I HLA Folding and Antigen Presentation in β2-Microglobulin-Defective Daudi Cells

Martayan¹,

Sibilio²,

Tremante³

et al. 2009

The Journal of Immunology

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To present virus and tumor Ags, HLA class I molecules undergo a complex multistep assembly involving discrete but transient folding intermediates. The most extensive folding abnormalities occur in cells lacking the class I L chain subunit, called β2-microglobulin (β2m). Herein, this issue was investigated taking advantage of eight conformational murine mAbs (including the prototypic W6/32 mAb) to mapped H chain epitopes of class I molecules, four human mAbs to class I alloantigens, as well as radioimmunoprecipitation, in vitro assembly, pulse-chase, flow cytometry, and peptide-pulse/ELISPOT experiments. We show that endogenous (HLA-A1, -A66, and -B58) as well as transfected (HLA-A2) heavy chains in β2m-defective Burkitt lymphoma Daudi cells are capable of being expressed on the cell surface, although at low levels, and exclusively as immature glycoforms. In addition, HLA-A2 is: 1) partially folded at crucial interfaces with β2m, peptide Ag, and CD8; 2) receptive to exogenous peptide; and 3) capable of presenting exogenous peptide epitopes (from virus and tumor Ags) to cytotoxic T lymphocytes (bulk populations as well as clones) educated in a β2m-positive environment. These experiments demonstrate a precursor-product relationship between novel HLA class I folding intermediates, and define a stepwise mechanism whereby distinct interfaces of the class I H chain undergo successive, ligand-induced folding adjustments in vitro as well as in vivo. Due to this unprecedented class I plasticity, Daudi is the first human cell line in which folding and function of class I HLA molecules are observed in the absence of β2m. These findings bear potential implications for tumor immunotherapy.

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Section: Discussionmentioning

confidence: 98%

Section: The ␤ 2 M-free Class I Heavy Chains Synthesized By Daudi Celmentioning

confidence: 99%

Section: Implications For Tumor Immune Surveillancementioning

confidence: 99%

mentioning

confidence: 99%

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Class I HLA Folding and Antigen Presentation in β2-Microglobulin-Defective Daudi Cells

Martayan¹,

Sibilio²,

Tremante³

et al. 2009

The Journal of Immunology

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“…No free HLA-A, -B, -C heavy chains have been detected at the surface of most β 2 m-defective cell lines described to date (Fellous et al, 1977;D'Urso et al, 1992;Gattoni-Celli et al, 1992;Wang et al, 1993;Bicknell et al, 1994;Porgador et al, 1997). In a recent report (Wang et al, 1998) the surface expression of HC-10-reacting, β 2 m-free HLA-A25 and -B8 heavy chains was detected in FO-1 cells. This, however, required treatment with IFN-α and hypothermia.…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of HLA-C heavy chains in melanoma cells with multiple defects in the expression of HLA-A, -B, -C molecules

et al. 1999

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Summary Recent investigations have shown that malignant transformation may down-regulate the expression of class I HLA molecules, β 2 -microglobulin (β 2 m) and members of the antigen-processing machinery. In the present study, we HLA-genotyped and identified at a biochemical level the three (HLA-A25, -B8, -Cw7) class I alleles expressed by the previously described [D'Urso CM et al (1992) J Clin Invest 87: 284-292] β 2 m-defective human melanoma FO-1 cell line and tested their ability to interact with calnexin, calreticulin and the TAP (transporter associated with antigen processing) complex. All these alleles were found to bind calnexin, but not calreticulin or the poorly expressed TAP complex, both in parental and β 2 m-transfected FO-1 cells, demonstrating a complex defect of class I expression in FO-1 cells. In these conditions, Cw7 heavy chains interacted with calnexin more strongly than A25 and B8, and preferentially accumulated in the endoplasmic reticulum, in both a calnexin-associated and a calnexin-free form. In addition, they could be transported to the cell surface at low levels even in the absence of β 2 m, without undergoing terminal glycosylation. These results establish a parallel between HLA-C and the murine D b and L d molecules which have been found to be surface expressed and functional in β 2 m-defective cells. They also demonstrate distinctive features of HLA-C molecules. We propose that the accumulation of several assembly intermediates of HLA-C might favour the binding of peptide antigens not readily bound by HLA-A and -B molecules in neoplastic cells with suboptimal class I expression.

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Modification of gene expression: Help to detect doping with erythropoiesis‐stimulating agents

Varlet‐Marie

Audran

Ashenden³

et al. 2009

American J Hematol

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Induction and functional characterization of β 2-microglobulin (β2-μ)-free HLA class I heavy chains expressed by β2-μ-deficient human FO-1 melanoma cells

Cited by 12 publications

References 34 publications

Class I HLA Folding and Antigen Presentation in β2-Microglobulin-Defective Daudi Cells

Class I HLA Folding and Antigen Presentation in β2-Microglobulin-Defective Daudi Cells

Biosynthesis of HLA-C heavy chains in melanoma cells with multiple defects in the expression of HLA-A, -B, -C molecules

Modification of gene expression: Help to detect doping with erythropoiesis‐stimulating agents

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