Abstract CD4 T cell help is critical for the activation of autoreactive CD8 T cells that cause most β-cell destruction in type-1 diabetes (T1D). We previously identified a 10 Mb C57BL/6 (B6)-origin recessive Idd susceptibility locus on chromosome 11, designated Idd32 that controls whether CD4 T cells cause pathogenic CD8 T cells to undergo activation or become tolerized. To identify the underlying gene, we adoptively transferred CD8 T cells transgenically expressing the diabetogenic AI4 T cell receptor into B6 mice expressing the NOD-derived H2g7 MHC haplotype (B6.H2g7) and one of 9 different NOD-derived segments of the Idd32 interval. This reduced the interval to a <520 kb region containing 18 polymorphic genes. To test these candidate genes (Δ) we used the CRISPR/Cas9 system to generate two sets of F1 strains: (B6.H2g7.Idd32NOD/NOD.Δ−/− x B6.H2g7)F1 and (B6.H2g7.Idd32NOD/NODx B6.H2g7)F1 that were monitored for T1D development after infusing them with AI4 T cells. We found that F1 mice lacking the NOD allele of the sialic acid transferase gene St6galnac1 (B6.H2g7.Idd32NOD/NOD. St6galnac1−/− x B6.H2g7)F1, but not other candidates, developed T1D. Furthermore, CD4 T cells from these mice strongly promoted diabetogenic AI4 T cell activation when co-transferred into NOD.Rag1−/− mice. In contrast, CD4 T cells from St6galnac1-intact (B6.H2g7.Idd32NOD/NODx B6.H2g7)F1 mice suppressed AI4 activation and T1D development. In summary, we have identified a novel, recessively-acting T1D susceptibility gene hidden in the normally T1D-resistant B6 mouse strain, with striking effects on pathogenic CD8 T cell activation. Our results may aid the screening of humans at future risk for T1D as well as provide a target for possible disease interventions.