Major histocompatibility complex-specific recognition of Mls-1 is mediated by multiple elements of the T cell receptor

Abstract

We have recently shown that recognition of the mouse mammary tumor virus 9-associated superantigen (vSAG-9) by murine Vβ17+ 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 Vβ and non-Vβ T cell receptor (TCR) elements. First, the influence of the Vβ element was apparent from the observation that Vβ8.2+ hybridomas were significantly more MHC specific in their recognition of Mls-1 than Vβ8.1 hybridomas. Second, a role for the TCR α chain was implicated from the distinct patterns of fine specificity of Mls-1 reactivity among a panel of transgenic hybridomas that expressed an identical β chain (Vβ8.1Dβ2Jβ2.3Cβ2). Sequence analysis revealed that junctional residues of the TCR α chain and/or Vα/Jα combinations influenced the MHC haplotype fine specificity for Mls-1. Third, DβJβ influences were implicated, in that the transgenic hybridomas expressed distinctive patterns of Mls-1 fine specificity not represented among Vβ8.1+ nontransgenic hybridomas. The findings that T cell recognition of endogenous superantigen is MHC specific, and that this specificity correlates with non-Vβ 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.