Mouse T lymphocyte response to acetylcholine receptor determined by T cell receptor for antigen Vβ gene products recognizing Mls-1^a

Mice of strain B6, but not AKR/J, respond to immunization with Torpedo acetylcholine receptor (AChR) by manifesting in vitro an Ag-specific T lymphocyte proliferative response. Our analysis of (AKR x B6)F₁ mice reveals that the T cell unresponsiveness of AKR/J is inherited as a dominant trait, possibly associated with expression of the Mls-1^a allele. Mice derived from backcrossing (AKR x B6)F₁ x B6 were selected for H-2^b homozygosity and were classified as Mls-1^a or Mls-1^b according to the relative numbers of peripheral blood T cells that expressed the TCR Vβ6 gene product. After challenge by injection with AChR in CFA, lymph node cells from mice classified as having <2% of Vβ6⁺ peripheral T cells had low responsiveness to AChR, whereas mice with >7% Vβ6⁺ peripheral T cells had high T cell responsiveness to AChR. These results are consistent with the notion that regulation of the T cell repertoire by Mls loci may be a determinant of susceptibility to autoimmunity.