Table 1.
TCR repertoires, antigens, and functions of unconventional lymphocyte subsets
| Cell type | TCR repertoire | Antigens | MHC restriction | Location | Phenotype/Cytokine profile | Specialized Functions |
|---|---|---|---|---|---|---|
| Invariant TCR | ||||||
| Vγ9Vδ2+ | Vγ9Vδ2 | phosphoantigens | none; require BTN3A1 | peripheral blood | antigen-experienced, IFNγ+, NK receptors | rapid IFNγ production elicited by parasitic infection, immune surveillance? |
| Tγδ17 | Vγ6Vδ1 and Vγ4Vδ5 (mouse) | ? | none | widespread (lymphoid, adipose, lung, liver, blood, etc) | immature, IL-17A+, NK receptors | rapid IL-17A production in response to broad range of pathogens and stimuli |
| DETCs | Vγ5Vδ1 (mouse) | Skint-1? | none | skin | dendritic morphology, antigen-experienced, IFNγ+, NK receptors | produce antimicrobial peptides and factors/cytokines aiding resolution of wound repair |
| γδ IELs | Vγ7Vδ4 (mouse) Vγ4+ (human) | Butyrophilins and Butyrophilin-like proteins | none | intestinal epithelium | antigen-experienced, IFNγ+, NK receptors | produce antimicrobial peptides and factors/cytokines aiding resolution of gut inflammation |
| iNKT | Vα14-Jα18 with Vβ7, 8.2, or 2 (mouse) Vα24-Jα15 with Vβ11 (human) | αGalCer and αGlcCer | CD1d | widespread (lymphoid, adipose, lung, liver, blood, etc) subsets enriched at different locations | antigen-experienced, IFNγ+, IL-17A+, IL-4+, NK receptors | early cytokine response in line with T helper profiles, B cell help. others? |
| MAIT | Vα19-Jα33 with Vβ6 or 8 (mouse) Vα7.2-Jα22/20 with Vβ2 or 6 (human) | modified riboflavin and folic acid intermediaries | MR1 | widespread (lymphoid, adipose, lung, liver, blood, etc) | antigen-experienced IFNγ+, IL-17A+, IL-4+ | early cytokine response and cytoxicity. others? |
| Diverse TCR | ||||||
| Vδ1+ γδ T cells | diverse CDR3δ paired with multiple TCRγ chains, oligoclonal | ?, sulfatide | multiple?, CD1d | peripheral blood, others? | antigen-experienced, IFNγ+ | CMV immunity, immune surveillance? |
| dNKT | diverse TCRα and TCRβ, oligoclonal | sulfatide, βGL1-22, LGL1 | CD1d | peripheral blood, others? | antigen-experienced, IFNγ+, NK receptors | ? |
| MR1T | diverse TCRα and TCRβ, oligoclonal | modified riboflavin and folic acid intermediaries | MR1 | peripheral blood, others? | antigen-experienced, IFNγ+ | ? |
| DN αβ IELs | diverse TCRα and TCRβ, oligoclonal | self-antigen? | Mixed. Require β2m and Tap1 | intestinal epithelium | “activated yet resting”, IFNγ+, cytotoxic, NK cell receptors | poorly understood, immune regulatory activity? |
| CD8 αβ IELs | diverse TCRα and TCRβ, oligoclonal | peptide antigens from pathogens, self-antigen? | MHC Ia | intestinal epithelium | effector memory, IFNγ+, cytotoxic, NK cell receptors | memory-like, cytotoxic |
| CD4 αβ IELs | diverse TCRα and TCRβ, oligoclonal | self-antigen? | MHC II | intestinal epithelium | effector memory, IFNγ+, NK receptors | memory-like, poorly understood |
Abbreviations: TCR, T cell receptor; MHC, major histocompatibility complex; BTN3A1, butyrophilin 3A1; DETCs, dendritic epidermal T cell; IEL, intraepithelial lymphocyte; NK, natural killer; iNKT, invariant natural killer T; αGalCer, α-galactosyl ceramide; αGlcCer, α-glucosylceramide; dNKT, diverse natural killer T; MAIT, mucosal-associated invariant T; MR1, MHC-related molecule-1; MR1T, MR1-restricted T; DN, double-negative; βGL1-22, β-glucosylceramide 22:0; LGL1, glucosylsphingosine
TCRγ and TCRδ V regions listed here follow the Tonegawa nomenclature