The J alpha segment contributes to the affinity of V beta 6+ cells for vSAG-7 (Mls-1a) presented by I-A molecules

Abstract

Recognition of superantigens (SAG) by T cells is major histocompatibility complex (MHC) dependent but not MHC restricted. In the case of vSAG-7 (Mls-1a), encoded by the Mtv-7 provirus, I-E molecules play a dominant role in the vSAG-7-MHC-T-cell receptor (TCR) interaction, the I-A molecule being less important. vSAG-7 is recognized predominantly by T cells bearing the V beta 6 element, which are deleted in Mtv-7+ mice; this deletion is nearly complete in mice expressing I-E molecules, but only partial in mice expressing exclusively the I-A molecules of permissive haplotypes. In view of these data, we hypothesized that vSAG-7-specific V beta 6+ T cells have a large spectrum of affinities for the MHC-vSAG-7 complex and that all of them, even those with a relatively low affinity, recognize the I-E-vSAG-7 complex, while only those with high affinity can recognize the I-A-vSAG-7 complex. Fourteen CD4 V beta 6+ vSAG-7-specific clones were studied and classified into three groups of avidity, depending on their interactions with different I-E- I-A(+)-vSAG-7 permissive haplotypes. Sequencing of the alpha and beta chains of their TCR suggested that the affinity for the vSAG-7 is influenced by the J alpha element. Four out of six low-affinity T-cell clones possessed the transcript for the J alpha 34 segment. Furthermore, five out of six low-affinity T-cell clones had the GGSN sequence in their CDR3 alpha, while the sixth low affinity clone had the conservative substituted SGGN sequence. These results strongly suggest that the expression of the J alpha 34 segment confers a very weak reactivity to T cells recognizing vSAG-7.