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. Author manuscript; available in PMC: 2016 Jan 1.
Published in final edited form as: Crit Rev Immunol. 2015;35(1):33–48. doi: 10.1615/critrevimmunol.2015012207

TABLE 1. Role of E and Id proteins in iNKT development.

E and Id proteins have recently been shown to play several roles in NKT TCR rearrangement, NKT lineage commitment, expansion, differentiation and maturation. Thus E and Id proteins regulate this lineage at several key NKT developmental steps which are marked in figure 1. Their functions at the different stages of NKT development are summarized in this table.

No. Developmental step E or Id protein role
1 Pre-TCR / β selection : DN3b stage

  • High E proteins suppress selection25
2 iNKT TCR rearrangement/ iNKT selection : DP stage

  • HEB promotes secondary rearrangement through increased survival23

  • Id3 prevents secondary rearrangement by turning off rag27

  • Id2 and Id3 prevent early Vα14-Jα18 rearrangement25
3 iNKT program initiation : iNKT Stage 0

  • E proteins bind to PLZF directly and promote expression26

  • Id protein deficiency lead to lower PLZF27
4 iNKT proliferation : mainly Stage 1

  • Id2 and Id3 limit iNKT proliferation25

  • Id3 limits iNKT numbers through all development stages26
5 iNKT subset differentiation: Stage 2

  • NKT1 development needs Id2 and Id3; NKT2 cells expand on Id3 deficiency26

  • NKT2 and NKT17 are supported by high E protein (or low Id proteins)28
6 iNKT Stage 3 maturation

  • Id3 needed at Stages 1 and 2 for initiating appropriate Stage 3 program27

  • E proteins prevent T-bet expression which is needed for maturation26