Yk. Chou et al., IMMUNITY TO TCR PEPTIDES IN MULTIPLE-SCLEROSIS .2. T-CELL RECOGNITIONOF V-BETA-5.2 AND V-BETA-6.1 CDR2 PEPTIDES, The Journal of immunology, 152(5), 1994, pp. 2520-2529
The biased expression of V beta 5.2 and V beta 6.1 by T cells specific
for myelin basic protein (BP) has led to our use of TCR peptides from
these V gene sequences to induce anti-TCR immunity in patients with m
ultiple sclerosis (MS). Injection of V beta 5.2-39-59 or V beta 6.1-39
-59 peptides significantly increased the peptide specific T cell frequ
ency in 7 of 11 MS patients, often with an accompanying delayed hypers
ensitivity reaction at the injection site. Here, we validate these cel
lular immune responses by characterizing TCR peptide specific T cells
from an MS patient with biased V beta 5.2 expression in BP reactive T
cells before treatment with TCR peptides, and from two MS patients in
whom the frequencies of anti-TCR peptide specific T cells were signifi
cantly boosted after injection with low doses of TCR peptides. In both
cases, T cell lines were established with relative ease, especially a
fter boosting with the peptides. A V beta 5.2-39-59 reactive line resp
onded selectively to the boosting peptide and was restricted by both M
HC class I (HLA-B7) and MHC class II (HLA-DR2) molecules. Characteriza
tion of 22 clonal isolates revealed that the responding T cells were p
redominantly activated CD4(+)CD8(lo), circulating memory cells restric
ted by either HLA-B7 or HLA-DR2, that utilized mainly V beta 4, V beta
6, V beta 12, and V beta 14, but not V beta 5.2 in their TCR. T cell
isolates specific for V beta 6.1-39-59 possessed similar characteristi
cs but contained specificities cross-reactive with an N-terminal seque
nce on V beta 5.2-39-59. Upon stimulation with peptide or Con A, the T
CR peptide specific T cell lines had increased message production for
IFN-gamma, GM-CSF, IL-4, IL-5, and to a lesser degree, IL-2. This lymp
hokine mRNA profile differed from a BP-specific T cell line that produ
ced message for IFN-gamma and GM-CSF but low or absent levels of IL-4
and IL-5. The extensive parallels between human T cells specific for V
beta 5.2 and V beta 6.1 CDR2 peptides and rat T cells specific for V
beta 8.2 CDR2 peptide that are highly protective against experimental
encephalomyelitis strengthen the rationale for the therapeutic use of
TCR peptides in human autoimmunity.