Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats: II. Biased T cell receptor Vβ expression predominates in spinal cord infiltrating T cells

The immune response of Lewis rat lymph node T cells to guinea pig myelin basic protein (GP-BP) in experimental allergic encephalomyelitis is directed primarily against a region of basic protein encompassed by residues 72-89. T cells that respond to this epitope are restricted by the RT1.B¹ class II molecule of the MHC and use Vβ8.2 exclusively in their TCR. A second region of GP-BP, residues 87-99, also induces experimental allergic encephalomyelitis in Lewis rats but this response is restricted primarily by RT1.D¹. Elsewhere we describe the biologic characteristics of T cell clones responding to the synthetic peptide, s87-99, and to a related peptide, s85-99. We present a detailed analysis of TCR Vβ gene expression among these clones, derived from the lymph node and spinal cord of immunized animals, and among spinal cord derived T cell clones reactive to GP-BP 72-89. We find that spinal cord-derived clones, reactive to s85-99 and to s87-99, use Vβ6 predominately. In contrast, T cell clones derived from lymph nodes and reactive to the same peptides express multiple Vβ genes including Vβ6. This difference in heterogeneity of Vβ usage at the clonal level is also seen in T cell lines derived from spinal cord and immune lymph node. DNA sequence comparison of the CDR3 regions in Vβ6⁺ spinal cord clones revealed a conserved amino acid motif also found in the majority of Vβ6 sequences from the spinal cord anti-s85-99 line. Although Vβ6 was expressed in some lymph node-derived clones, only one contained a CDR3 region similar to that seen in spinal cord isolates. All spinal cord-derived T cell clones reactive to GP-BP 72-89 used Vβ8.2 and most (five of six) contained the AspSer residues in CDR3 previously shown to be associated with Vβ8.2 receptors expressed by the majority of lymph node T cells responding to GP-BP 72-89. These data indicate that TCR Vβ usage in peripheral T cells responding to an autoantigen does not always predict the Vβ usage among T cells at the site of an autoimmune attack. Possible explanations for the relative homogeneity in TCR Vβ expression seen in T cell clones derived from the spinal cord are discussed.