Mar 2, 1993 - proteins), whereas biologically relevant T-helper-cell responses ... vesicular stomatitis virus exhibits more T-helper-cell than CTL epitopes.
Vol. 67, No. 6
JOURNAL OF VIROLOGY, June 1993, p. 3680-3683
0022-538X/93/063680-04$02.00/0 Copyright © 1993, American Society for MicrobiologY
Fewer Protective Cytotoxic T-Cell Epitopes Than T-HelperCell Epitopes on Vesicular Stomatitis Virus THOMAS M. KUNDIG,* IRENE CASTELMUR, MARTIN F. BACHMANN, DIANA ABRAHAM, DANIEL BINDER, HANS HENGARTNER, AND ROLF M. ZINKERNAGEL Institute of Experimental Immunology, University of Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland Received 13 November 1992/Accepted 2 March 1993
Cytotoxic T-lymphocyte (CTL) and T-helper-cell responses in various mouse strains were monitored. Protective CTL responsiveness against three proteins of vesicular stomatitis virus was H-2 linked and inducible only in half of the 15 combinations tested (each of five H-2 haplotypes combined with each of three viral proteins), whereas biologically relevant T-helper-cell responses were inducible in all. This suggests that vesicular stomatitis virus exhibits more T-helper-cell than CTL epitopes.
The immune system protects the host against an enormous variety of pathogens. Complete immunological cytotoxic T-lymphocyte (CTL) nonresponsiveness has been demonstrated only for very few viruses (10). One example is vesicular stomatitis virus (VSV), for which H-2-linked CTL nonresponsiveness has been demonstrated in H-2k mice (14). In this study, various mouse strains were monitored for their capacity to mount biologically relevant CD8+ CTL, CD4+ T-helper-cell, and B-cell responses against each of three VSV proteins, namely, the nucleoprotein of VSV serotype Indiana (VSV-IND-N), the glycoprotein of VSV serotype Indiana (VSV-IND-G), and the glycoprotein of VSV serotype New Jersey (VSV-NJ-G). The main functions of CTLs are the elimination of viruses during primary infection and antiviral protection against reinfection (2, 9). Whether a primary infection with VSV wild type (wt) induced antivirally protective CTL memory was tested by challenging VSV wt-immune mice with vaccinia recombinant viruses expressing one of the three VSV proteins to be tested. Protection against such a challenge infection has been shown to correlate exclusively with the T-cell response induced by infection with VSV wt (1). Anti-VSV antibodies play no role in eliminating the vaccinia recombinant viruses because vaccinia recombinant viruses do not incorporate the recombinant gene products into their envelopes (20). The timing and the dose of the challenge infection were chosen so that the sensitivity for detecting protective T-cell memory was maximal. Ten days after the priming infection with VSV wt, the primary CTL response, which peaks on day 6, has declined (18) and protective T-cell memory should be maximal. The intracerebral challenge dose of 2 x 103 PFU of vaccinia recombinant virus was found to be the minimal dose that constantly replicates in unprimed mice (data not shown). H-2-linked CTL nonresponsiveness is frequently found. The mouse strains listed in Table 1 were primed with VSV-IND wt (Mudd-Summers isolate) or VSV-NJ wt (Pringle isolate) (2 x 106 PFU intravenously [i.v.]). After 10 days, mice were challenged intracerebrally with the vaccinia recombinant viruses vacc-IND-N, vacc-IND-G, or vacc-NJ-G (8) (2 x 103 PFU in 30 ,ul). If VSV wt infection had induced a T-cell *
response, the respective vaccinia recombinant viruses were usually eliminated below detection levels by day 5 (
0
=
I11 Ii I0 II IIr 00~~~~~~~~ w " -4 00 IC
~~
___~~ ___
QAA
LA
AA CD
0 0 0 0 _Z __ _1 ___
I+ I+ I+RI+
o
AA
Uh~~~~-~
1~~~~ t -F _ _ °41 ~~~ LI)§O
ol+
()
i-
_v
v
&
I+I+
I+ I+ I+ I+ co VV VV V V O tw O~ C O ov~~~~ CD CD 0 0 CD Cw O O JCDC) (Z) C w ~-CA _, tS, 00'o £~12 _12
~0.4OOtAA r0
I+
I+
0
0
ACA
-o
-
A
-
t
I+
1+I+1++ I
I++
1+I+
A0
000
00
0
I I
I I
I II IA
t
Dc
_
_
£ UCA
Cl
0C0
~oao
P
-4--4Cb~0 -.4.~ C
.0C~0
.~0
Q~ 0
1+1+1+ 1+1+11+
1+1+
1+O
000 0000
00
I
.0.~~00
V IV
00
V
-- ... . ***.
£~~~.
.*
o 0 f
0' 00 0~we CA
CA
-JC
-o.J
