Analysis of T cell antigen receptors of myelin basic protein specific T cells in SJL/J mice demonstrates an alpha chain CDR3 motif associated with encephalitogenic T cells.
Experimental autoimmune encephalomyelitis (EAE) is an animal autoimmune disease mediated by CD4+ T cells. Analysis of TCR expression revealed 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 haplotype and Lewis rats. The usage of a particular beta chain complementarity determining region 3 (CDR3) motif has also been shown. However, it remains unclear to what extent these observations can be extrapolated. 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 reaction on reverse transcribed mRNA. Although the V beta usage was less restricted than in H-2u mice, they predominantly utilized V beta 17a and expressed LGG or related motifs in the V beta-D beta-J beta junctions. Furthermore, a single alpha chain rearrangement between V alpha 1.1 and J alpha BBM142 with no N region diversity was preferentially used. Concordantly, immunization with a peptide corresponding to the alpha chain CDR3 was found to significantly alter the clinical course of EAE. Comparison of the published TCR junctional regions demonstrates that the CDR3 motifs (LGG in beta chain, CA*R*NY motif in alpha chains) are expressed by other encephalitogenic clones. Notably, the CA*R*NY was conserved in PL/J mice clones that recognize a distinct MBP-MHC determinant. It suggests that an antigen-independent mechanism may contribute to conserving the alpha chain motif. The implications of these observations are discussed.
Yamamura
T
T
Department of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.
Kondo
T
T
Sakanaka
S
S
Kozovska
M
M
Geng
T C
TC
Takahashi
K
K
Tabira
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*
D007135:Immunoglobulin Variable Region; D004676:Myelin Basic Protein; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta