MAJOR HISTOCOMPATIBILITY COMPLEX SPECIFIC RECOGNITION OF MLS-1 IS MEDIATED BY MULTIPLE ELEMENTS OF THE T-CELL RECEPTOR

We have recently shown that recognition of the mouse mammary tumor virus 9-associated superantigen (vSAG-9) by murine Vbeta17+ T cells is strongly influenced by the major histocompatibility complex (MHC) class II haplotype of the presenting cells, resulting in a form of MHC-restricted recognition. This finding was unexpected, because T cell recognition of another well-characterized retroviral superantigen, minor lymphocyte-stimulating antigen 1 (Mls-1), had been shown to be independent of the MHC haplotype of the presenting cell. To determine whether recognition of vSAG-9 and Mls-1 is fundamentally different, we undertook an extensive analysis of MHC haplotype influences on vSAG-9 and Mls-1 recognition by panels of T cell hybridomas. Our results show that, although most hybridomas recognized Mls-1 regardless of the MHC haplotype of the presenting cells, as previously described by others, some hybridomas exhibited unique patterns of MHC fine specificity. Thus, T cell recognition of vSAG-9 and Mls-1 is not fundamentally different, but the apparent differences can be explained in terms of frequency. The MHC fine specificity of individual Mls-1-reactive hybridomas was influenced by both Vbeta and non-Vbeta T cell receptor (TCR) elements. First, the influence of the Vbeta element was apparent from the observation that Vbeta8.2+ hybridomas were significantly more MHC specific in their recognition of Mls-1 than Vbeta8.1 hybridomas. Second, a role for the TCR alpha chain was implicated from the distinct patterns of fine specificity of Mls-1 reactivity among a panel of transgenic hybridomas that expressed an identical beta chain (Vbeta8.1Dbeta2Jbeta2.3Cbeta2). Sequence analysis revealed that junctional residues of the TCR alpha chain and/or Valpha/Jalpha combinations influenced the MHC haplotype fine specificity for Mls-1. Third, DbetaJbeta influences were implicated, in that the transgenic hybridomas expressed distinctive patterns of Mls-I fine specificity not represented among Vbeta8.1+ nontransgenic hybridomas. The findings that T cell recognition of endogenous superantigen is MHC specific, and that this specificity correlates with non-Vbeta elements of the TCR, support the hypothesis that there is a direct interaction between the TCR and either polymorphic residues of the MHC class II molecule or haplotype-specific dominant peptides presented by class II.