Identification of Key Amino Acids of the Mouse Mammary Tumor Virus Superantigen Involved in the Specific Interaction with T-cell Receptor V(beta) Domains

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2001 Jul 20

PMID 11462017

Citations 2

Authors

F Baribaud

S Wirth

I Maillard

S Valsesia

H Acha-Orbea

H DIGGELMANN

Affiliations

Soon will be listed here.

Abstract

Mouse mammary tumor virus (MMTV) is a retrovirus encoding a superantigen that is recognized in association with major histocompatibility complex class II by the variable region of the beta chain (V(beta)) of the T-cell receptor. The C-terminal 30 to 40 amino acids of the superantigen of different MMTVs display high sequence variability that correlates with the recognition of particular T-cell receptor V(beta) chains. Interestingly, MMTV(SIM) and mtv-8 superantigens are highly homologous but have nonoverlapping T-cell receptor V(beta) specificities. To determine the importance of these few differences for specific V(beta) interaction, we studied superantigen responses in mice to chimeric and mutant MMTV(SIM) and mtv-8 superantigens expressed by recombinant vaccinia viruses. We show that only a few changes (two to six residues) within the C terminus are necessary to modify superantigen recognition by specific V(beta)s. Thus, the introduction of the MMTV(SIM) residues 314-315 into the mtv-8 superantigen greatly decreased its V(beta)12 reactivity without gain of MMTV(SIM)-specific function. The introduction of MMTV(SIM)-specific residues 289 to 295, however, induced a recognition pattern that was a mixture of MMTV(SIM)- and mtv-8-specific V(beta) reactivities: both weak MMTV(SIM)-specific V(beta)4 and full mtv-8-specific V(beta)11 recognition were observed while V(beta)12 interaction was lost. The combination of the two MMTV(SIM)-specific regions in the mtv-8 superantigen established normal MMTV(SIM)-specific V(beta)4 reactivity and completely abolished mtv-8-specific V(beta)5, -11, and -12 interactions. These new functional superantigens with mixed V(beta) recognition patterns allowed us to precisely delineate sites relevant for molecular interactions between the SIM or mtv-8 superantigen and the T-cell receptor V(beta) domain within the 30 C-terminal residues of the viral superantigen.

Citing Articles

Prevalent de novo somatic mutations in superantigen genes of mouse mammary tumor viruses in the genome of C57BL/6J mice and its potential implication in the immune system.

Lee Y, Chiu S, Chew A, Greenhalgh D, Cho K BMC Immunol. 2011; 12:5.

PMID: 21244697 PMC: 3038982. DOI: 10.1186/1471-2172-12-5.

Regions of mouse mammary tumor virus superantigen involved in interaction with the major histocompatibility complex class II I-A molecule.

Wirth S, Vessaz A, Krummenacher C, Baribaud F, Acha-Orbea H, Diggelmann H J Virol. 2002; 76(21):11172-5.

PMID: 12368363 PMC: 136634. DOI: 10.1128/jvi.76.21.11172-11175.2002.

References

Waanders G, Lussow A, MacDonald H . Skewed T cell receptor V alpha repertoire among superantigen reactive murine T cells. Int Immunol. 1993; 5(1):55-61. DOI: 10.1093/intimm/5.1.55. View

HELD W, Shakhov A, Izui S, Waanders G, Scarpellino L, MacDonald H . Superantigen-reactive CD4+ T cells are required to stimulate B cells after infection with mouse mammary tumor virus. J Exp Med. 1993; 177(2):359-66. PMC: 2190911. DOI: 10.1084/jem.177.2.359. View

HELD W, Waanders G, Shakhov A, Scarpellino L, Acha-Orbea H, MacDonald H . Superantigen-induced immune stimulation amplifies mouse mammary tumor virus infection and allows virus transmission. Cell. 1993; 74(3):529-40. DOI: 10.1016/0092-8674(93)80054-i. View

Tomonari K, Fairchild S, Rosenwasser O, Tada N . The Ly45.1 alloantigen: preferential expression on CD4(-)CD8(-)/CD4(+)CD8(+) thymocytes. Immunogenetics. 1998; 48(4):292-5. DOI: 10.1007/s002510050434. View

Maillard I, Xenarios I, DIGGELMANN H, Orbea H . Differential reactivity of TCR Vbeta10 alleles to a mouse mammary tumor virus superantigen. Eur J Immunol. 1998; 28(10):3075-85. DOI: 10.1002/(SICI)1521-4141(199810)28:10<3075::AID-IMMU3075>3.0.CO;2-6. View

Baribaud F, Shaw A, Scarpellino L, DIGGELMANN H, Acha-Orbea H . Preferential binding of mouse mammary tumor virus to B lymphocytes. J Virol. 1999; 73(9):7899-902. PMC: 104325. DOI: 10.1128/JVI.73.9.7899-7902.1999. View

Krummenacher C, DIGGELMANN H . The mouse mammary tumor virus long terminal repeat encodes a 47 kDa glycoprotein with a short half-life in mammalian cells. Mol Immunol. 1993; 30(13):1151-7. DOI: 10.1016/0161-5890(93)90133-v. View

Gold D, Surh C, Sellins K, Schroder K, Sprent J, Wilson D . Rat T cell responses to superantigens. II. Allelic differences in V beta 8.2 and V beta 8.5 beta chains determine responsiveness to staphylococcal enterotoxin B and mouse mammary tumor virus-encoded products. J Exp Med. 1994; 179(1):63-9. PMC: 2191313. DOI: 10.1084/jem.179.1.63. View

Bellio M, Lone Y, de la Calle-Martin O, Malissen B, Abastado J, Kourilsky P . The V beta complementarity determining region 1 of a major histocompatibility complex (MHC) class I-restricted T cell receptor is involved in the recognition of peptide/MHC I and superantigen/MHC II complex. J Exp Med. 1994; 179(4):1087-97. PMC: 2191438. DOI: 10.1084/jem.179.4.1087. View

10.

Herrmann T, Hochgrebe T, Huber B, Hunig T . Control of the rat T cell response to retroviral and bacterial superantigens by class II MHC products and Tcrb-V8.2 alleles. J Immunol. 1994; 152(9):4300-9. View

11.

Braun M, Jouvin-Marche E, Marche P, MacDonald H, Acha-Orbea H . T cell receptor V beta repertoire in mice lacking endogenous mouse mammary tumor provirus. Eur J Immunol. 1995; 25(3):857-62. DOI: 10.1002/eji.1830250334. View

12.

Krummenacher C, DIGGELMANN H, Acha-Orbea H . In vivo effects of a recombinant vaccinia virus expressing a mouse mammary tumor virus superantigen. J Virol. 1996; 70(5):3026-31. PMC: 190162. DOI: 10.1128/JVI.70.5.3026-3031.1996. View

13.

Maillard I, Erny K, Acha-Orbea H, DIGGELMANN H . A V beta 4-specific superantigen encoded by a new exogenous mouse mammary tumor virus. Eur J Immunol. 1996; 26(5):1000-6. DOI: 10.1002/eji.1830260507. View

14.

Le Bon A, Lucas B, Vasseur F, Penit C, PAPIERNIK M . In vivo T cell response to viral superantigen. Selective migration rather than proliferation. J Immunol. 1996; 156(12):4602-8. View

15.

Hong S, Waterbury G, Janeway Jr C . Different superantigens interact with distinct sites in the Vbeta domain of a single T cell receptor. J Exp Med. 1996; 183(4):1437-46. PMC: 2192526. DOI: 10.1084/jem.183.4.1437. View

16.

Garcia K, Degano M, Stanfield R, Brunmark A, Jackson M, Peterson P . An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science. 1996; 274(5285):209-19. DOI: 10.1126/science.274.5285.209. View

17.

Liao L, Marinescu A, Molano A, Ciurli C, Sekaly R, Fraser J . TCR binding differs for a bacterial superantigen (SEE) and a viral superantigen (Mtv-9). J Exp Med. 1996; 184(4):1471-82. PMC: 2192839. DOI: 10.1084/jem.184.4.1471. View

18.

Fields B, Malchiodi E, Li H, Ysern X, Stauffacher C, Schlievert P . Crystal structure of a T-cell receptor beta-chain complexed with a superantigen. Nature. 1996; 384(6605):188-92. DOI: 10.1038/384188a0. View

19.

Asmuss A, Hofmann K, Hochgrebe T, Giegerich G, Hunig T, Herrmann T . Alleles of highly homologous rat T cell receptor beta-chain variable segments 8.2 and 8.4: strain-specific expression, reactivity to superantigens, and binding of the mAb R78. J Immunol. 1996; 157(10):4436-41. View

20.

Luther S, Acha-Orbea H . Mouse mammary tumor virus: immunological interplays between virus and host. Adv Immunol. 1997; 65:139-243. View