CLEC11A and CLEC2B mediate tumor surveillance through HLA-V and KIR2DL3.

We describe here a function of CLEC11A and CLEC2B in tumor surveillance through HLA-V and KIR2DL3. HLA-V distinguished KIR2DL3+ cell fractions: Kir family receptors were induced or repressed together with HLA-V. Slamf6 was silenced, as was FNDC3A. Both Clec11a and Clec2b were activated. Other Clec family receptors were involved in tumor surveillance through HLA-V and KIR2DL3 including C-type lectin receptors of the Clec18 family and Clec4A. Fam43A and Ano9 marked these cells, together with NCR3. Fam223A/B expression was shared, as was Fam226A/B, Fam247C/D, Gpr34 and Gpr82. Clec11a and Clec2b signaling involved the functions of Icoslg and LILR receptors LILRA1/2 and LILRB2/3. Lymphocyte antigen family receptors were, consistent with previous description of HLA-V function, important for Clec11a and Clec2b signaling; Ly9 was modest induced in KIR2DL3hi cells while Ly6E was expressed in large quantity but not significantly different in KIR2DL3(hi) and KIR2DL3(lo) cells. Thus, CLEC11A and CLEC2B function as co-receptors in tumor surveillance through HLA-V and KIR2DL3.