Unconventional T Cell Targets for Cancer Immunotherapy Dale I. Godfrey, Jérôme Le Nours, Daniel M. Andrews, Adam P. Uldrich, Jamie Rossjohn  Immunity  Volume 48, Issue 3, Pages 453-473 (March 2018) DOI: 10.1016/j.immuni.2018.03.009 Copyright © 2018 Elsevier Inc. Terms and Conditions

Figure 1 Unconventional T Cell Types Unconventional T cells, divided into groups based on their restriction elements. 5-OP-RU, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil; 6-FP, 6-formylpterin; Ag, antigen; a-GalCer, a-galactosylceramide; DDM, dideoxymycobactin; GEM, germline-encoded mycolyl lipid-reactive; GMM, glucose monomycolate; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; mLPA, methyl lysophosphatidic acid; MAIT, mucosal-associated invariant T; NKT, natural killer T; PG, phosphatidylglycerol; PM, phosphomycoketide; ? = insufficient or very limited data; 1, H2-M3 and Qa-2 restricted T cells are mouse only; 2, human TCR sequences shown; 3, only human gd T cells shown. Immunity 2018 48, 453-473DOI: (10.1016/j.immuni.2018.03.009) Copyright © 2018 Elsevier Inc. Terms and Conditions

Figure 2 CD1-Restricted Lipid-Based Ags (A) shows a cartoon of a type I NKT cell recognizing α-GalCer presented by a CD1d+ Ag presenting cell. The ternary crystal structure of the TCR-CD1d-α-GalCer complex is shown in the inset. (B) shows a sample of synthetic lipid analogs that have the ability to provide enhanced and/or Th1-biased type I NKT cell responses. (C) shows examples of tumor-derived lipid Ags that are capable of being recognized by CD1d-restricted T cells, with the exception of mLPA that is recognized by CD1c-restricted T cells. α-GalCer, α-galactosylceramide; mLPA, methyl lysophosphatidic acid; NKT, natural killer T. Immunity 2018 48, 453-473DOI: (10.1016/j.immuni.2018.03.009) Copyright © 2018 Elsevier Inc. Terms and Conditions

Figure 3 MR1-Restricted Vitamin B Metabolite Ags (A) shows a cartoon of a MAIT cell recognizing a vitamin B metabolite presented by an MR1+ Ag presenting cell. The ternary crystal structure of the MAIT TCR-MR1-Ag complex is shown in the inset. (B) shows some examples of vitamin-B derivative Ags that have the ability to bind to MR1 and, with varying degrees of potency, to stimulate MAIT cells via their TCR. The exceptions are 6-FP and Acetyl-6-FP (Ac-6-FP) which bind MR1, but are not stimulatory for the majority of MAIT cells. 5-OP-RU, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil; 6-FP, 6-formylpterin; Ag, antigen; MAIT, mucosal-associated invariant T. Immunity 2018 48, 453-473DOI: (10.1016/j.immuni.2018.03.009) Copyright © 2018 Elsevier Inc. Terms and Conditions