scholarly journals Deletion of CD4+T Cells by Mouse Mammary Tumor Virus (FM) Superantigen with Broad Specificity of T Cell Receptor β-Chain Variable Region

Virology ◽  
1996 ◽  
Vol 223 (2) ◽  
pp. 387-391 ◽  
Author(s):  
Takayuki Yoshimoto ◽  
Hisashi Nagase ◽  
Hideki Nakano ◽  
Akio Matsuzawa ◽  
Hideo Nariuchi
Keyword(s):  
T Cells ◽  
T Cell Receptor ◽  
Mouse Mammary Tumor Virus ◽  
Variable Region ◽  
Cell Receptor ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Β Chain ◽  
Broad Specificity

scholarly journals Identification of Key Amino Acids of the Mouse Mammary Tumor Virus Superantigen Involved in the Specific Interaction with T-Cell Receptor Vβ Domains

2001 ◽  
Vol 75 (16) ◽  
pp. 7453-7461 ◽  
Author(s):  
Frédéric Baribaud ◽  
Susanne Wirth ◽  
Ivan Maillard ◽  
Sandrine Valsesia ◽  
Hans Acha-Orbea ◽  
...  
Keyword(s):  
Amino Acids ◽  
T Cell ◽  
T Cell Receptor ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Specific Interaction ◽  
Cell Receptor ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

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 (Vβ) 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 Vβ chains. Interestingly, MMTV(SIM) andmtv-8 superantigens are highly homologous but have nonoverlapping T-cell receptor Vβ specificities. To determine the importance of these few differences for specific Vβ 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 Vβs. Thus, the introduction of the MMTV(SIM) residues 314-315 into themtv-8 superantigen greatly decreased its Vβ12 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 Vβ reactivities: both weak MMTV(SIM)-specific Vβ4 and fullmtv-8-specific Vβ11 recognition were observed while Vβ12 interaction was lost. The combination of the two MMTV(SIM)-specific regions in the mtv-8superantigen established normal MMTV(SIM)-specific Vβ4 reactivity and completely abolished mtv-8-specific Vβ5, -11, and -12 interactions. These new functional superantigens with mixed Vβ recognition patterns allowed us to precisely delineate sites relevant for molecular interactions between the SIM or mtv-8 superantigen and the T-cell receptor Vβ domain within the 30 C-terminal residues of the viral superantigen.

scholarly journals Superantigen-reactive CD4+ T cells are required to stimulate B cells after infection with mouse mammary tumor virus.

1993 ◽  
Vol 177 (2) ◽  
pp. 359-366 ◽  
Author(s):  
W Held ◽  
A N Shakhov ◽  
S Izui ◽  
G A Waanders ◽  
L Scarpellino ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Large Fraction ◽  
Cell Receptor ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

Superantigens are defined by their ability to stimulate a large fraction of T cells via interaction with the T cell receptor (TCR) V beta domain. Endogenous superantigens, classically termed minor lymphocyte-stimulating (Mls) antigens, were recently identified as products of open reading frames (ORF) in integrated proviral copies of mouse mammary tumor virus (MMTV). We have described an infectious MMTV homologue of the classical endogenous superantigen Mls-1a (Mtv-7). The ORF molecules of both the endogenous Mtv-7 and the infectious MMTV(SW) interact with T cells expressing the TCR V beta 6, 7, 8.1, and 9 domains. Furthermore, the COOH termini of their ORF molecules, thought to confer TCR specificity, are very similar. Since successful transport of MMTV from the site of infection in the gut to the mammary gland depends on a functional immune system, we were interested in determining the early events after and requirements for MMTV infection. We show that MMTV(SW) infection induces a massive response of V beta 6+ CDC4+ T cells, which interact with the viral ORF. Concomitantly, we observed a B cell response and differentiation that depends on both the presence and stimulation of the superantigen-reactive T cells. Furthermore, we show that B cells are the main target of the initial MMTV infection as judged by the presence of the reverse-transcribed viral genome and ORF transcripts. Thus, we suggest that MMTV infection of B cells leads to ORF-mediated B-T cell interaction, which maintains and possibly amplifies viral infection.

scholarly journals Peripheral T cell activation and deletion induced by transfer of lymphocyte subsets expressing endogenous or exogenous mouse mammary tumor virus.

1993 ◽  
Vol 177 (5) ◽  
pp. 1359-1366 ◽  
Author(s):  
G A Waanders ◽  
A N Shakhov ◽  
W Held ◽  
O Karapetian ◽  
H Acha-Orbea ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Lymphocyte Subsets ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Cell Deletion

Murine T cell reactivity with products of the minor lymphocyte stimulatory (Mls) locus correlates with the expression of particular variable (V) domains of the T cell receptor (TCR) beta chain. It was recently demonstrated that Mls antigens are encoded by an open reading frame (ORF) in the 3' long terminal repeat of either endogenous or exogenous mouse mammary tumor virus (MMTV). Immature thymocytes expressing reactive TCR-V beta domains are clonally deleted upon exposure to endogenous Mtv's. Mature T cells proliferate vigorously in response to Mls-1a (Mtv-7) in vivo, but induction of specific anergy and deletion after exposure to Mtv-7-expressing cells in the periphery has also been described. We show here that B cells and CD8+ (but not CD4+) T cells from Mtv-7+ mice efficiently induce peripheral deletion of reactive T cells upon transfer to Mtv-7- recipients, whereas only B cells stimulate specific T cell proliferation in vivo. In contrast to endogenous Mtv-7, transfer of B, CD4+, or CD8+ lymphocyte subsets from mice maternally infected with MMTV(SW), an infectious homologue of Mtv-7, results in specific T cell deletion in the absence of a detectable proliferative response. Finally, we show by secondary transfers of infected cells that exogenous MMTV(SW) is transmitted multidirectionally between lymphocyte subsets and ultimately to the mammary gland. Collectively our data demonstrate heterogeneity in the expression and/or presentation of endogenous and exogenous MMTV ORF by lymphocyte subsets and emphasize the low threshold required for induction of peripheral T cell deletion by these gene products.

scholarly journals A Novel Block to Mouse Mammary Tumor Virus Infection of Lymphocytes in B10.BR Mice

2007 ◽  
Vol 82 (3) ◽  
pp. 1314-1322 ◽  
Author(s):  
Chioma M. Okeoma ◽  
Ming Shen ◽  
Susan R. Ross
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Cell Activation ◽  
Mouse Strains ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Mhc Locus

ABSTRACT Classic studies on C57BL-derived mouse strains showed that they were resistant to mouse mammary tumor virus (MMTV) infection. Although one form of resistance mapped to the major histocompatibility complex (MHC) locus, at least one other, unknown gene was implicated in this resistance. We show here that B10.BR mice, which are derived from C57BL mice but have the same MHC locus (H-2 k ) as susceptible C3H/HeN mice, are resistant to MMTV, and show a lack of virus spread in their lymphoid compartments but not their mammary epithelial cells. Although in vivo virus superantigen (Sag)-mediated activation of T cells was similar in C3H/HeN and B10.BR mice, T cell-dependent B-cell and dendritic cell activation was diminished in the latter. Ex vivo, B10.BR T cells showed a diminished capacity to proliferate in response to the MMTV Sag. The genetic segregation of the resistance phenotype indicated that it maps to a single allele. These data highlight the role of Sag-dependent T-cell responses in MMTV infection and point to a novel mechanism for the resistance of mice to retroviral infection that could lead to a better understanding of the interplay between hosts and pathogens.

scholarly journals Highly Biased CDR3 Usage in Restricted Sets of β Chain Variable Regions During Viral Superantigen 9 Response

1998 ◽  
Vol 187 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Cristina Ciurli ◽  
David N. Posnett ◽  
Rafick-Pierre Sékaly ◽  
François Denis
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Hypervariable Region ◽  
Cell Receptor ◽  
Variable Regions ◽  
Cdr3 Region ◽  
Tumor Virus ◽  
The One ◽  
Β Chain

Superantigens encoded by the mouse mammary tumor virus can stimulate a large proportion of T cells through interaction with germline-encoded regions of the T cell receptor β chain like the hypervariable region 4 (HV4) loop. However, several lines of evidence suggest that somatically generated determinants in the CDR3 region might influence superantigen responses. We stimulated T cells from donors differing at the BV6S7 allele with vSAG9 to assess the nature and structure of the T cell receptor in amplified T cells and to evaluate the contribution of non-HV4 elements in vSAG recognition. This report demonstrates that vSAG9 stimulation caused the expansion of TCR BV6-expressing T cells, although to varying degrees depending on the BV6 subfamily. The BV6S7 subfamily was preferentially expanded in all donors, but in donors homozygous for the BV6S7*2 allele, a significant number of BV6S5 T cells were amplified and showed a highly biased β chain junctional region (BJ) and CDR3 usage. As CDR3 regions are involved in major histocompatibility complex (MHC)–peptide interaction, such a selection is highly suggestive of an intimate MHC–TCR interaction and would imply that the topology of the MHC-vSAG-TCR complex is similar to the one occurring during conventional antigen recognition.

scholarly journals Reverse transcriptase-dependent and -independent phases of infection with mouse mammary tumor virus: implications for superantigen function.

1994 ◽  
Vol 180 (6) ◽  
pp. 2347-2351 ◽  
Author(s):  
W Held ◽  
G A Waanders ◽  
H Acha-Orbea ◽  
H R MacDonald
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Clonal Expansion ◽  
Local Immune Response ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

Mouse mammary tumor virus (MMTV) encodes a superantigen (SAg) that promotes stable infection and virus transmission. Upon subcutaneous MMTV injection, infected B cells present SAg to SAg-reactive T cells leading to a strong local immune response in the draining lymph node (LN) that peaks after 6 d. We have used the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (AZT) to dissect in more detail the mechanism of SAg-dependent enhancement of MMTV infection in this system. Our data show that no detectable B or T cell response to SAg occurs in AZT pretreated mice. However, if AZT treatment is delayed 1-2 d after MMTV injection, a normal SAg-dependent local immune response is observed on day 6. Quantitation of viral DNA in draining LN of these infected mice indicates that a 4,000-fold increase in the absolute numbers of infected cells occurs between days 2 and 6 despite the presence of AZT. Furthermore MMTV DNA was found preferentially in surface IgG+ B cells of infected mice and was not detectable in SAg-reactive T cells. Collectively our data suggest that MMTV infection occurs preferentially in B cells without SAg involvement and is completed 1-2 d after virus challenge. Subsequent amplification of MMTV infection between days 2 and 6 requires SAg expression and occurs in the absence of any further requirement for reverse transcription. We therefore conclude that clonal expansion of infected B cells via cognate interaction with SAg-reactive T cells is the predominant mechanism for increasing the level of MMTV infection. Since infected B cells display a memory (surface IgG+) phenotype, both clonal expansion and possibly longevity of the virus carrier cells may contribute to stable MMTV infection.

scholarly journals The effects of chronic infection with a superantigen-producing virus.

1992 ◽  
Vol 175 (4) ◽  
pp. 917-923 ◽  
Author(s):  
L Ignatowicz ◽  
J Kappler ◽  
P Marrack
Keyword(s):  
T Cells ◽  
Mammary Tumor ◽  
Cd4 T Cells ◽  
Chronic Infection ◽  
Mouse Mammary Tumor Virus ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

C3H/HeJ mice transmit a mouse mammary tumor virus from mother to pup in milk. The retrovirus infects mice shortly after birth and, when expressed in recipient mice, produces a V beta 14-specific superantigen. The consequences of such expression on V beta 14-bearing T cells are examined in this paper. Most cells bearing V beta 14 and either CD4 or CD8 are eliminated in the thymus. Some V beta 14-bearing cells escape to the periphery, however. Those bearing CD8 are unaffected by expression of the viral superantigen. The percentage of peripheral CD4+ T cells bearing V beta 14 drops with time after birth. In large part this seems to be due to the fact that many of these cells become anergic because of exposure to the viral superantigen. Unlike normal T cells, these anergic cells cannot undergo peripheral postthymic expansion. Consequently, they drop in percentage even during a time when their total numbers are constant.

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