ANALYSIS OF T-CELL ANTIGEN RECEPTORS OF MYELIN BASIC-PROTEIN SPECIFICT-CELLS IN SJL J MICE DEMONSTRATES AN ALPHA-CHAIN CDR3 MOTIF ASSOCIATED WITH ENCEPHALITOGENIC T-CELLS/
T. Yamamura et al., ANALYSIS OF T-CELL ANTIGEN RECEPTORS OF MYELIN BASIC-PROTEIN SPECIFICT-CELLS IN SJL J MICE DEMONSTRATES AN ALPHA-CHAIN CDR3 MOTIF ASSOCIATED WITH ENCEPHALITOGENIC T-CELLS/, International immunology, 6(7), 1994, pp. 947-954
Experimental autoimmune encephalomyelitis (EAE) is an animal autoimmun
e disease mediated by CD4+ T cells. Analysis of TCR expression reveale
d that limited TCR elements (V(beta)8.2, V(alpha)2 or 4) were utilized
by myelin basic protein (MBP) specific T cells in mice with H-2u hapl
otype and Lewis rats. The usage of a particular beta chain complementa
rity determining region 3 (CDR3) motif has also been shown. However, i
t remains unclear to what extent these observations can be extrapolate
d. Here we studied the TCR sequences of MBP 89 - 101/I-A(s) specific T
cell clones derived from SJL/J mice, using the polymerase chain react
ion on reverse transcribed mRNA. Although the V(beta) usage was less r
estricted than in H-2u mice, they predominantly utilized V(beta)17a an
d expressed LGG or related motifs in the V(beta) - D(beta) - J(beta) j
unctions. Furthermore, a single alpha chain rearrangement between V(al
pha)1.1 and J(alpha)BBM142 with no N region diversity was preferential
ly used. Concordantly, immunization with a peptide corresponding to th
e alpha chain CDR3 was found to significantly alter the clinical cours
e of EAE. Comparison of the published TCR junctional regions demonstra
tes that the CDR3 motifs (LGG in beta chain, CAR*NY motif in alpha ch
ains) are expressed by other encephalitogenic clones. Notably, the CA
RNY was conserved in PL/J mice clones that recognize a distinct MBP -
MHC determinant. It suggests that an antigen-independent mechanism ma
y contribute to conserving the alpha chain motif. The implications of
these observations are discussed.