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Modulation of major histocompatibility complex antigen expression by human immunodeficiency virus-2 gp36
Immunology Letters 68 (1999) 415 – 417
Rapid note
Modulation of major histocompatibility complex antigen expression by human immunodeficiency virus-2 gp36 Ying-Hua Chen a,*, Yun Bai a, Tianwei Yu a, Manfred P. Dierich b a
Laboratory of Immunology, School of Life Science and Engineering, Tsinghua Uni6ersity, Beijing 100084, People’s Republic of China b Institute of Hygiene, Uni6ersity of Innsbruck, Ludwig-Boltzmann-lnstitute for AlDS-Research, A-6020 Innsbruck, Austria Received 8 January 1999; accepted 15 February 1999
Keywords: MHC antigen; HIV-2; CD4
The human immunodeficiency virus type I (HIV-I) after binding by the envelope gpl20 to its cellular receptor CD4 and co-receptor fusin or CC-CKR-S (chemokine receptor) infects susceptible cells [1]. It was demonstrated by the authors and others that a putative cellular receptor for HIV-1 gp41 binding exists on human T, B lymphoctes and monocytes [2 – 5]. Two binding sites for gp41 binding to cells were located in both regions (aa 583 – 599 and 641 – 675) [2 – 4]. Recent studies have found an increased levels of antibodies recognizing interferon (IFN)-a and -b in HIV-I infected individuals and a common immunological epitope existing between the first binding site (aa 583 – 599) on gp41 and a region on human type I interferons [6 – 8]. It was observed that gp41 could up-regulate cell surface expression of the major histocompatibility complex (MHC) on human B cell line Raji [9]. It was observed by the authors that HIV-2 gp36 like HIV-I gp41 could bind to human T, B lymphocytes and monocytes [10,11]. Recently, a strong amino acid sequence similarity was found between HIV-2 gp36 and HIV-I gp41 at the two binding sites. The first binding site (aa 565–581 in gp36 and aa 583 – 599 in gp41) shows 86.7% sequence similarity, and a 15-amino acid residues region (aa 637 – 651 in gp36 and aa 659 – 673 in gp41) in the center of the second binding site shows 66.7% sequence similarity. Based on these findings, effect of HIV-2 gp36 on modulation MHC expression
* Corresponding author. Tel.: + 86-10-62789385; fax: + 86-1062785505. E-mail address: [email protected] (Y.-H. Chen)
on the human B cell line Raji was examined. The recombinant soluble gp36 (rsgp36, Env aa 518– 678 from clone HIV 2ROD) obtained from Biotest GmbH (Germany) represents the external portion of the transmembrane protein gp36 of HIV-2. Raji cells were treated by 5 mg/ml gp36 for 48 h at 37°C in a 5% CO2 atmosphere. In flow cytometry analysis, it was found that rsgp36 could enhance MHC class I antigen expression on Raji cells by about 160% (Fig. 1). The regulation effect is selective and specific because rsgp36 could not modulate expression of other cell surface molecules, such as MHC class II (data not shown). Though rsgp36 could bind to human T, B lymphocytes and monocytes [10], rsgp36 did not modulate MHC antigen expression on human CD4 + T cell line H9 and monocyte cell line U937 (data not shown). The up-regulation effect of rsgp36 on MHC class I expression on Raji cells could be inhibited by mouse antiserum against rsgp36 and interestingly by mouse antiserum to human IFN-p (Fig. 1), while normal mouse serum did not. The inhibition effect of the anti-IFN-p serum may be based on its activity recognizing the first binding site, because it was demonstrated that the anti-IFN-,B serum could recognize the first binding site [11]. A variety of cytokines, particularly IFNs, have been shown to increase MHC expression [12]. Some viruses can up- or down-regulate MHC expression. but the mechanisms appear to be interferon-independent [13]. The exact mechanism(s) of rsgp36-induced enhancement of Raji MHC class I antigen expression has not been fully elucidated.
0165-2478/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S 0 1 6 5 - 2 4 7 8 ( 9 9 ) 0 0 0 6 5 - 6
416
Y.-H. Chen et al. / Immunology Letters 68 (1999) 415–417
Fig. 1. Modulation of major histocompatibility complex (MHC) class I antigen expression on Raji cells by recombinant soluble gp36 (rsgp36) in flow cytometry assay. (a) Relative fluorescence intensity (mean values). AS(gp36), mouse anti-gp36 antiserum (1:100 diluted); AS(IFN-b), mouse anti-lFN-b antiserum; NS, normal mouse serum. (b) Fluorescence activated cell sorter (FACS)-histogram overlays: curve 1, negative control (PBS-treated cells stained only with FITC-conjugated rabbit anti-mouse Ig without anti-MHC class I antibody; curve 2, PBS-treated cells stained with anti-NIHC class I antibody; curve 3, rsgp36-treated cells stained with anti-MHC class I antibody; curve 4, inhibition of up-regulation effect of rsgp36 by mouse anti-gp36 antiserum: curve 5, inhibition of up-regulation effect of rsgp36 by mouse anti-1FN-b antiserum.
Y.-H. Chen et al. / Immunology Letters 68 (1999) 415–417
Acknowledgements This study was supported by the NSFC-39770696 and NSFC-39000043.
References [1] J. Binley, J.P. Moore, Nature (Lond.) 387 (1997) 346. [2] Y.H. Chen, C. Ebenbichler, R. Vornhagen, et al., AIDS 6 (1992) 533. [3] Y.H. Chen, M.P. Dierich, Immunol. Lett. 50 (1996) 153. [4] L.A. Henderson, M.N. Qureshi, J. Biol. Chem. 268 (1993) 15291.
.
417
[5] Y.H. Chen, G. Bo¨ck, R. Vornhagen, et al., Immunobioiogy 188 (1993) 323. [6] Y.H. Chen, H. Stoiber, M.P. Dierich, Immunol. Lett. 55 (1997) 15. [7] Y.H. Chen, J.N. Feng, G. Stockl, et al., Mol. Immunol. 34 (1998) 1259. [8] Y.H. Chen, M.P. Dierich, Immunol. Today 19 (1998) 586. [9] Y.H. Chen, G. Bo¨ck, R. Vornhagen, et al., Mol. Immunol. 31 (1994) 977. [10] C. Ebenbichler, C. Roder, R. Vornhagen, et al., AIDS 7 (1993) 489. [11] Y.H. Chen, A. Christiansen, G. Bo¨ck, M.P. Dierich, AIDS 9 (1995) 1193. [12] Y.H. Chen, M.P. Dierich, Immunobiology 198 (1998) 333. [13] P.F. Halloran, A. Wadgymar, P. Autenried, Transplantation 41 (1986) 413.
Rapid note
Modulation of major histocompatibility complex antigen expression by human immunodeficiency virus-2 gp36 Ying-Hua Chen a,*, Yun Bai a, Tianwei Yu a, Manfred P. Dierich b a
Laboratory of Immunology, School of Life Science and Engineering, Tsinghua Uni6ersity, Beijing 100084, People’s Republic of China b Institute of Hygiene, Uni6ersity of Innsbruck, Ludwig-Boltzmann-lnstitute for AlDS-Research, A-6020 Innsbruck, Austria Received 8 January 1999; accepted 15 February 1999
Keywords: MHC antigen; HIV-2; CD4
The human immunodeficiency virus type I (HIV-I) after binding by the envelope gpl20 to its cellular receptor CD4 and co-receptor fusin or CC-CKR-S (chemokine receptor) infects susceptible cells [1]. It was demonstrated by the authors and others that a putative cellular receptor for HIV-1 gp41 binding exists on human T, B lymphoctes and monocytes [2 – 5]. Two binding sites for gp41 binding to cells were located in both regions (aa 583 – 599 and 641 – 675) [2 – 4]. Recent studies have found an increased levels of antibodies recognizing interferon (IFN)-a and -b in HIV-I infected individuals and a common immunological epitope existing between the first binding site (aa 583 – 599) on gp41 and a region on human type I interferons [6 – 8]. It was observed that gp41 could up-regulate cell surface expression of the major histocompatibility complex (MHC) on human B cell line Raji [9]. It was observed by the authors that HIV-2 gp36 like HIV-I gp41 could bind to human T, B lymphocytes and monocytes [10,11]. Recently, a strong amino acid sequence similarity was found between HIV-2 gp36 and HIV-I gp41 at the two binding sites. The first binding site (aa 565–581 in gp36 and aa 583 – 599 in gp41) shows 86.7% sequence similarity, and a 15-amino acid residues region (aa 637 – 651 in gp36 and aa 659 – 673 in gp41) in the center of the second binding site shows 66.7% sequence similarity. Based on these findings, effect of HIV-2 gp36 on modulation MHC expression
* Corresponding author. Tel.: + 86-10-62789385; fax: + 86-1062785505. E-mail address: [email protected] (Y.-H. Chen)
on the human B cell line Raji was examined. The recombinant soluble gp36 (rsgp36, Env aa 518– 678 from clone HIV 2ROD) obtained from Biotest GmbH (Germany) represents the external portion of the transmembrane protein gp36 of HIV-2. Raji cells were treated by 5 mg/ml gp36 for 48 h at 37°C in a 5% CO2 atmosphere. In flow cytometry analysis, it was found that rsgp36 could enhance MHC class I antigen expression on Raji cells by about 160% (Fig. 1). The regulation effect is selective and specific because rsgp36 could not modulate expression of other cell surface molecules, such as MHC class II (data not shown). Though rsgp36 could bind to human T, B lymphocytes and monocytes [10], rsgp36 did not modulate MHC antigen expression on human CD4 + T cell line H9 and monocyte cell line U937 (data not shown). The up-regulation effect of rsgp36 on MHC class I expression on Raji cells could be inhibited by mouse antiserum against rsgp36 and interestingly by mouse antiserum to human IFN-p (Fig. 1), while normal mouse serum did not. The inhibition effect of the anti-IFN-p serum may be based on its activity recognizing the first binding site, because it was demonstrated that the anti-IFN-,B serum could recognize the first binding site [11]. A variety of cytokines, particularly IFNs, have been shown to increase MHC expression [12]. Some viruses can up- or down-regulate MHC expression. but the mechanisms appear to be interferon-independent [13]. The exact mechanism(s) of rsgp36-induced enhancement of Raji MHC class I antigen expression has not been fully elucidated.
0165-2478/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S 0 1 6 5 - 2 4 7 8 ( 9 9 ) 0 0 0 6 5 - 6
416
Y.-H. Chen et al. / Immunology Letters 68 (1999) 415–417
Fig. 1. Modulation of major histocompatibility complex (MHC) class I antigen expression on Raji cells by recombinant soluble gp36 (rsgp36) in flow cytometry assay. (a) Relative fluorescence intensity (mean values). AS(gp36), mouse anti-gp36 antiserum (1:100 diluted); AS(IFN-b), mouse anti-lFN-b antiserum; NS, normal mouse serum. (b) Fluorescence activated cell sorter (FACS)-histogram overlays: curve 1, negative control (PBS-treated cells stained only with FITC-conjugated rabbit anti-mouse Ig without anti-MHC class I antibody; curve 2, PBS-treated cells stained with anti-NIHC class I antibody; curve 3, rsgp36-treated cells stained with anti-MHC class I antibody; curve 4, inhibition of up-regulation effect of rsgp36 by mouse anti-gp36 antiserum: curve 5, inhibition of up-regulation effect of rsgp36 by mouse anti-1FN-b antiserum.
Y.-H. Chen et al. / Immunology Letters 68 (1999) 415–417
Acknowledgements This study was supported by the NSFC-39770696 and NSFC-39000043.
References [1] J. Binley, J.P. Moore, Nature (Lond.) 387 (1997) 346. [2] Y.H. Chen, C. Ebenbichler, R. Vornhagen, et al., AIDS 6 (1992) 533. [3] Y.H. Chen, M.P. Dierich, Immunol. Lett. 50 (1996) 153. [4] L.A. Henderson, M.N. Qureshi, J. Biol. Chem. 268 (1993) 15291.
.
417
[5] Y.H. Chen, G. Bo¨ck, R. Vornhagen, et al., Immunobioiogy 188 (1993) 323. [6] Y.H. Chen, H. Stoiber, M.P. Dierich, Immunol. Lett. 55 (1997) 15. [7] Y.H. Chen, J.N. Feng, G. Stockl, et al., Mol. Immunol. 34 (1998) 1259. [8] Y.H. Chen, M.P. Dierich, Immunol. Today 19 (1998) 586. [9] Y.H. Chen, G. Bo¨ck, R. Vornhagen, et al., Mol. Immunol. 31 (1994) 977. [10] C. Ebenbichler, C. Roder, R. Vornhagen, et al., AIDS 7 (1993) 489. [11] Y.H. Chen, A. Christiansen, G. Bo¨ck, M.P. Dierich, AIDS 9 (1995) 1193. [12] Y.H. Chen, M.P. Dierich, Immunobiology 198 (1998) 333. [13] P.F. Halloran, A. Wadgymar, P. Autenried, Transplantation 41 (1986) 413.