Analysis of T cell antigen receptors of myelin basic protein specific T cells in SJL/J mice demonstrates an α chain CDR3 motif associated with encephalitogenic T cells

Abstract

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.

High frequencies of identical T cell clonotypes in synovial tissues of rheumatoid arthritis patients suggest the occurrence of common antigen‐driven immune responses

“…In patient RAI, as shown in Table 2, 3 possible motifs in the CDR3 regions, G-X-G, LG, and GR, could be postulated, although a high frequency of glycine residues is a common feature of all TCR CDR3 regions. These 3 motifs were also different from those of the dominant motifs in multiple sclerosis (46) and experimental allergic encephalomyelitis (47)(48)(49)(50). Even more notably, predominant usage of the J& 1 gene segment was found (7 of 13 TCR V, genes tested used the J,2.1 gene).…”

An ?-chain TCR CDR3 peptide can enhance EAE induced by myelin basic protein or proteolipid protein

“…, 1994). cells in Lewis rats (Gold et al, 1991;Zhang and HeberKatz, 1992) and SJL/J mice (Yamamura et al, 1994). In addition, a regulatory effect of VP-DP-JS junctional sequences from MBP-specific T cells was previously reported in rats (Howell et al, 1989).…”

“…Studies have revealed that MBP-specific encephalitogenic T cells are characterized by restricted usage of particular T cell receptor (TCR) gene elements (Rcha-Orbea et al, 1988;Urban et al, 1988;Burns et al, 1989;Yamamura et al, 1994). It has also been established that spontaneous recovery from EAE involves regulatory immunity against TCR sequences shared by encephalitogenic T cells Kumar and Sercarz, 1993;Kumar et al, 1995), and that this regulation could be tightened by administration of appropriate TCR peptides Howell et al, 1989;Stevens et al, 1992;Vainiene et al, 1992;Kumar et al, 1995).…”

T Cells With Similar T-Cell Receptor β-Chain Complementarity-Determining Region 3 Motifs Infiltrate Inflammatory Lesions of Synthetic Peptides Inducing Rat Autoimmune Myocarditis

“…Therefore, in one EAM rat a few clones of myocarditogenic T cells may be activated, and in another EAM rat a few other clones of myocarditogenic T cells may be activated. T cell clones that were cultivated by the same antigenic peptide were reported to have different kinds of TCR with similar CDR3, 25 and in recent studies, it was reported that contact with TCR and antigenic peptide in the context major histocompatibility was not strict and that a kind of T-cell clone could respond to several antigenic peptides. 26 The present study is compatible with those reports.…”