A common TCR V-D-J sequence in V beta 13.1 T cells recognizing an immunodominant peptide of myelin basic protein in multiple sclerosis.
T cell responses to the immunodominant peptide (residues 83-99) of myelin basic protein are potentially associated with multiple sclerosis (MS). This study was undertaken to examine whether a common sequence motif(s) exists within the TCR complementarity-determining region (CDR)-3 of T cells recognizing the MBP83-99 peptide. Twenty MBP83-99-reactive T cell clones derived from patients with MS were analyzed for CDR3 sequences, which revealed several shared motifs. Some V beta 13.1 T cell clones derived from different patients with MS were found to contain an identical CDR3 motif, V beta 13.1-LGRAGLTY. Oligonucleotides complementary to the shared CDR3 motifs were used as specific probes to detect identical target CDR3 sequences in a large panel of T cell lines reactive to MBP83-99 and unprimed PBMC. The results revealed that, in contrast to other CDR3 motifs examined, the LGRAGLTY motif was common to T cells recognizing the MBP83-99 peptide, as evident by its expression in the majority of MBP83-99-reactive T cell lines (36/44) and PBMC specimens (15/48) obtained from randomly selected MS patients. The motif was also detected in lower expression in some PBMC specimens from healthy individuals, suggesting the presence of low precursor frequency of T cells expressing this motif in healthy individuals. This study provides new evidence indicating that the identified LGRAGLTY motif is preferentially expressed in MBP83-99-reactive T cells. The findings have important implications in monitoring and targeting MBP83-99-reactive T cells in MS.
Hong
J
J
Multiple Sclerosis Research Laboratory, Department of Neurology, Baylor-Methodist International Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX 77030, USA.
Zang
Y C
YC
Tejada-Simon
M V
MV
Kozovska
M
M
Li
S
S
Singh
R A
RA
Yang
D
D
Rivera
V M
VM
Killian
J K
JK
Zhang
J Z
JZ
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002999:Clone Cells; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004274:DNA, Recombinant / Q000302:isolation & purification; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D017931:DNA Primers; D004274:DNA, Recombinant; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C104448:myelin basic protein 83-99