A TCR V alpha CDR3-specific motif associated with Lewis rat autoimmune encephalomyelitis and basic protein-specific T cell clones.
To investigate TCR V alpha gene expression in the Lewis rat model of experimental autoimmune encephalomyelitis, we obtained V alpha chain sequences from two V beta8.2+-encephalitogenic, BP72-89-specific T cell clones. Two different V alpha genes, a V alpha2 gene and a V alpha23 gene, are utilized, but both were found to contain an asparagine repeat (Asn3+) sequence present in the V alpha CDR3 region. This Asn3+ motif is also present in the previously reported sequence of a BP68-88-specific hybridoma, 510, which utilizes a different V alpha2 gene family member. In further experiments, spinal cord T cells were isolated at the onset of basic protein (BP)-induced disease and sorted for the OX-40 activation marker, which we have previously used to enrich for specifically activated T cells. Analysis of V alpha expression in the OX-40+ population revealed the biased use of three V alpha genes, V alpha1, V alpha2, and V alpha23. The Asn3+ motif was present in the V alpha CDR3 region of V alpha1, V alpha2, and V alpha23 cDNA derived from OX-40+ spinal cord T cells but found to be generally absent in the OX-40- spinal cord population. Since these Asn3+ motif-bearing V alpha chain sequences are nearly identical to those utilized by the BP-specific encephalitogenic clones described, it is likely that these V alpha sequences are derived from disease-associated T cells in the spinal cord. Thus, we demonstrate that the Asn3+ V alpha CDR3 motif is strongly associated with experimental autoimmune encephalomyelitis in the Lewis rat and propose that it plays a role in TCR recognition of a specific BP peptide/MHC complex.
Buenafe
A C
AC
Department of Neurology, Oregon Health Sciences University, Portland 97201, USA.
Tsu
R C
RC
Bebo
B
B
Bakke
A C
AC
Vandenbark
A A
AA
Offner
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D017421:Sequence Analysis; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D015704:CD4 Antigens; D007135:Immunoglobulin Variable Region; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta