TY - JOUR
T1 - Response of human T lymphocyte lines to myelin basic protein
T2 - Association of dominant epitopes with HLA class II restriction molecules
AU - Chou, Y. K.
AU - Vainiene, M.
AU - Whitham, R.
AU - Bourdette, D.
AU - Chou, C. H.‐J
AU - Hashim, G.
AU - Offner, H.
AU - Vandenbark, A. A.
PY - 1989/6
Y1 - 1989/6
N2 - In animals, the selection in vitro of T cell lines to myelin basic protein (MBP) can define immunodominant and encephalitogenic epitopes which are preferentially associated with class II major histocompatibility (MHC) molecules. These principles were used to evaluate the specificity and MHC restriction of 14 human MBP‐reactive T cell lines selected from normal individuals and patients with multiple sclerosis (MS) and other neurological diseases (OND). The four normal T cell lines recognized single, separate immunodominant MBP epitopes which were restricted by MHC molecules from the DR or in one case the DP class II locus. In contrast, the MS and OND T cell lines recognized multiple MBP epitopes, each in association with a discrete class II MHC molecule from the DR or DQ locus. Overall, HLA‐DR molecules were used preferentially to associate with epitopes on human MBP, restricting 26/33 responses. As predicted from animal studies, T cells from genetically disparate individuals responded to different immunodominant epitopes on human MBP in association with distinct MHC class II molecules. HLA‐DR2, which is overrepresented in MS patients, possessed an unusual capacity to restrict all eight epitopes identified on MBP in this study. These data provide the first evidence of genetically restricted human T cell recognition of potentially encephalitogenic epitopes of MBP.
AB - In animals, the selection in vitro of T cell lines to myelin basic protein (MBP) can define immunodominant and encephalitogenic epitopes which are preferentially associated with class II major histocompatibility (MHC) molecules. These principles were used to evaluate the specificity and MHC restriction of 14 human MBP‐reactive T cell lines selected from normal individuals and patients with multiple sclerosis (MS) and other neurological diseases (OND). The four normal T cell lines recognized single, separate immunodominant MBP epitopes which were restricted by MHC molecules from the DR or in one case the DP class II locus. In contrast, the MS and OND T cell lines recognized multiple MBP epitopes, each in association with a discrete class II MHC molecule from the DR or DQ locus. Overall, HLA‐DR molecules were used preferentially to associate with epitopes on human MBP, restricting 26/33 responses. As predicted from animal studies, T cells from genetically disparate individuals responded to different immunodominant epitopes on human MBP in association with distinct MHC class II molecules. HLA‐DR2, which is overrepresented in MS patients, possessed an unusual capacity to restrict all eight epitopes identified on MBP in this study. These data provide the first evidence of genetically restricted human T cell recognition of potentially encephalitogenic epitopes of MBP.
KW - T cell lines
KW - epitope specificity
KW - human myelin basic protein
KW - immunodominance
UR - http://www.scopus.com/inward/record.url?scp=0024334453&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024334453&partnerID=8YFLogxK
U2 - 10.1002/jnr.490230211
DO - 10.1002/jnr.490230211
M3 - Article
C2 - 2474079
AN - SCOPUS:0024334453
SN - 0360-4012
VL - 23
SP - 207
EP - 216
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 2
ER -