Tumour Specific Transplantation Antigen in Hamster Tumour Cells

Tumour Specific Transplantation Antigen in Hamster Tumour Cells

I7I J. gen. Virol. 0978), 4I, 171-174 Printed in Great Britain Tumour Specific Transplantation Antigen in Hamster Tumour Cells Induced with BK Virus...

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I7I

J. gen. Virol. 0978), 4I, 171-174 Printed in Great Britain

Tumour Specific Transplantation Antigen in Hamster Tumour Cells Induced with BK Virus (Accepted 9 M a y I978) SUMMARY

Immunization of hamsters with purified BK virus (BKV) followed by transplantation of BKV-induced hamster turnout cells revealed a tumour specific transplantation antigen (TSTA) in these cells. The antigen did not cross-react with the TSTA of SV4o since immunization with BKV did not protect against challenge of SV4o tumour cells. BK virus (BKV), a human polyoma virus, transforms rodent cells in vitro (Major & Di Mayorca, I973; Portolani et al. I975) and induces tumours in hamsters (Ngse et al. I975; Shah et al. I975). It shares minor virion antigen components with other viruses of the polyoma-SV4o subgroup of papovaviruses (Penney & Narayan, 1973). In addition, T antigen present in cells infected or transformed with BKV cross-reacts strongly with the T antigen of SV4o and JC virus, by immunofluorescent staining. The latter virus is another human polyoma virus which also induces tumours in hamsters (Walker et al. I973). Cells transformed by SV4o or by JC virus contain a tumour-specific transplantation antigen (TSTA), and it has been shown that the TSTA of these two viruses are mutually distinct (Padgett et al. I977). Furthermore, immunization of hamsters with BKV before transplantation of SV4o or JC virus-transformed cells did not confer protection against tumour growth (Padgett et al. I977). We have previously reported induction of tumours in hamsters with BKV, and described some characteristics of cell lines derived from these tumours (Sten et al. I976). Since it has not been previously shown, we were interested in finding out whether BKV-induced hamster tumour cells also contained a TSTA, and whether immunity against BKV TSTA would give any protection against SV4o tumour cells. BKV was purified from a medium of infected Vero cells (M~intyj/irvi et al. 1972). Viruscontaining medium was concentrated tenfold by vacuum dialysis (Biofiber; Bio-Rad, California). Virus was pelleted through 20 % (w/v) sucrose solution in tris-buffered saline, pH 7"5, by ultracentrifugation (1o0o0o g for 9o min), treated with receptor destroying enzyme (Cholera Filtrate, N.V. Philips Duphar, Holland) and banded in a CsC1 gradient (iooooog for I8 h). Fractions containing full virus particles were pooled, dialysed, and used for immunization. The virus concentration of the pools was 2.o to 6"4 x Io4 haemagglutinating units/ml. The inbred strain of hamsters used for immunization was the same as that from which the BKV tumour cells were obtained (LSH; Lake View Hamster Colony, New Jersey). After varying immunization schedules, hamsters were challenged by subcutaneous injections of BKV or SV4o turnout cells. The origin of the BKV tumour cells (BKT cell lines) and of the SV4o turnout cells (H-5o/LSHz ceils) has been described previously (Sten et al. I976). Three to five different doses of these cells were injected into groups of three to eight hamsters. Hamsters were examined twice weekly for Iz weeks. The median tumourproducing dose of transplanted cells (TPDso) was calculated (Reed & Muench, I938)

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Short communications

17 2

Table I. Effect o f immunization with B K V on transplantation

o f B K V tumour cells in hamsters Experiment

Immunogen

I

BKV -BKV -BKV -BKV

2

3 4

Age when immunized (weeks)

Challenge tumour cells

o, 4 and 8

BKT-2C BKT-2C BKT-zA BKT-2A BKT-2A BKT-zA BKT-2C BKT-2C

4, 5 and 6 o, 2 and 4 o, 2 and 4

--

Resistance index

TPDs0

6

2"5 × IO5 4"2 X IO4 5"9 × I& 7"6 X IOa 5"0 x io 5 6.0 x [ o ~ 5"9 x I&

78 83 12

5"1 X IO z

Table 2. Growth o f SV4o and BKV-induced tumour cells in

hamsters immunized with B K V Weeks after challenge r

Group

Immunogen

I

BKV

2

3

Challenge tumour cells

Number of tumour cells injected

2'o 3"5 4"0 4"5 5"5 Tumour growth index c

H-5o/LSH2

--

BKV

--

H-5o/LSH~

BKT-IB

BKT-IB

Io6 lO5

8

I8

o

4

31 32 4 I 7

13

19

10 4

O

0

2

IO

15

10 3

0

0

0

0

0

1o6

8 18 27 33 38

I&

o

3

4

9

I 0 'I

0

2

2

2

6

IO a

0

O

0

0

0

1o6

o

o

3

8

Io

10 6

0

0

0

2

2

I0 ~ 10 3

0 0

0 0

0 0

0 0

0 0

IO 6

0

8

13

18

10 5

O

O

0

3

10 4

0

O

O

2

2

I0 a

0

O

O

0

0

II

II

8

the resistance index (RI) expressed as a ratio of TPDso of i m m u n i z e d animals to TPDs0 of n o n - i m m u n i z e d animals. The t u m o u r growth index was calculated according to Barra

et al.

0977).

T a b l e I shows the results of four separate experiments. I m m u n i z e d a n d n o n - i m m u n i z e d control hamsters were challenged with t u m o u r cells 2 to 3 weeks after the last i m m u n i z a tion. The resistance index calculated 5 to 9 weeks after challenge was only 6 in experiment i. I n subsequent experiments, however, R I values above Io were obtained, which is considered to be the limit of significance (Tevethia et al. I97~). I n a further experiment hamsters were again i m m u n i z e d with B K V a n d challenged I week after the last i m m u n i z a t i o n with B K T - I B as well as with H - 5 o / L S H 2 cells. The i m m u n i z a t i o n schedule was the same as in experiment 3.:_Tumour growth indices at various times after challenge are shown in Table 2. I m m u n i z a t i o n with B K V did n o t give a n y protection against H - 5 o / L S H 2 cells, whereas h o m o l o g o u s i m m u n i t y against B K V t u m o u r cells was, again, present. I n the groups receiving Io 6 B K T - I B challenge cells in which the n u m b e r of t u m o u r s p r o d u c e d was high e n o u g h for a reliable comparison, the difference between growth indices of i m m u n i z e d a n d n o n -

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Short communications

t73

immunized hamsters was significant at a level of o.oi > P > o.ooi (Student's t test for paired observations). Our results indicate that transformation by BKV induces an antigen which can be detected by a transplantation rejection test. The variation in RI is probably an indication of a different immunosensitivity of the tumour cell lines used. The transplantation antigen of BKV is comparable to the TSTA of SV4o and JC virus. Like the TSTA of JC virus, the TSTA of BKV did not cross-react with the TSTA of SV4o. Therefore our results together with those reported by others (Takemoto & Mullarkey, I973; Shah et al. I975; Padgett et al. I977) show that each of the three viruses, SV4o, JC and BKV has a distinct TSTA. On the other hand, immunization with JCV or BKV-transformed hamster cells protected mice against a challenge of SV4o-induced mouse tumour cells (Law et al. 1977). It was also reported by Molinaro et al. (I977) that, by using an in vitro technique, common surface antigens were found in cells transformed by SV4o and BKV. In both of these cases the immunization was performed in a heterologous species which might recognize antigens not immunogenic in a syngeneic system. The distinctiveness of the TSTA of SV4o, JC and BKV is a very interesting phenomenon because of the immunological similarity of the T antigens of the same viruses (Takemoto & Mullarkey, I973; Walker et al. 1973)- TSTA and T antigen are both coded for by the same, early region of virus DNA. Differences in tryptic peptides of T antigens of SV4o and BKV may explain the presence of specific TSTA if both antigenic determinants are located in the same polypeptide (Rundell et al. 1977; Simmons et al. 1977). Post-translational modification of the primary early protein (A protein) or transcription of two mRNAs in different phases from early DNA region are two possible explanations for having T and TSTA determinants on separate molecules. The latter possibility would be comparable to the relationship between VPI and VP2/VP3 of SV4o (Contreras et al. I977)This work was supported by the Academy of Finland and by Sigrid Jus61ius Foundation. H. E. KARJALAINEN A. M. LAAKSONEN R. A. M.~NTYJ~RVI

Department of Clinical Microbiology University of Kuopio 7oioo Kuopio, Io Finland REFERENCES

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(Received 5 January J978)

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