The Innate Biologies of Adaptive Antigen Receptors

Abstract

Nonclonal innate immune responses mediated by germ line–encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic recombination. However, the Variable (V) regions of antigen receptors include germ line–encoded motifs unaltered by somatic recombination, and theoretically available to mediate nonclonal, innate responses, that are independent of or largely override clonotypic responses. Recent evidence demonstrates that such responses exist, underpinning the associations of particular γδ T cell receptors (TCRs) with specific anatomical sites. Thus, TCRγδ can make innate and adaptive responses with distinct functional outcomes. Given that αβ T cells and B cells can also make nonclonal responses, we consider that innate responses of antigen receptor V-regions may be more widespread, for example, inducing states of preparedness from which adaptive clones are better selected. We likewise consider that potent, nonclonal T cell responses to microbial superantigens may reflect subversion of physiologic innate responses of TCRα/β chains.

ABCA1/ABCB1 Ratio Determines Chemo- and Immune-Sensitivity in Human Osteosarcoma

“…This result is in line with previous findings showing that Vγ9Vδ2 T-cells infiltrating the tumors may vary independently from other T-lymphocyte subsets [57]. Indeed Vγ9Vδ2 T-cells recognize different antigens and mount a different immune-response from CD4 + and CD8 + T-lymphocytes [12,14,15].…”

“…γδ T-lymphocytes peculiarly recognize non-major histocompatible complex (MHC) antigens, structurally characterized by a phosphate moieties (phosphoantigens) [14]. They mount a fast immune response, with intermediate features between innate and adaptive immunity [12,15]. Different subsets of γδ T-cells, producing different cytokines, may have pro-tumor or anti-tumor effects [12,14].…”

T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion

“…Furthermore, these unconventional T cells also include T cells bearing γδ TCRs, which mediate antigen recognition in an MHC-unrestricted process that, to this date, is still poorly understood, since the identity of γδ TCR antigens is largely unclear [ 26 ]. However, recent evidence in the past decade provided some clarity and suggests that it involves butyrophilin (BTN) or BTN-like (BTNL) molecules, which are related to the B7 co-stimulatory molecules, CD80 and CD86 [ 26 , 27 , 28 ]. Furthermore, antigen recognition by γδ T cells also appears to be quite promiscuous, since they can also engage MR1 [ 29 ], CD1 variants [ 30 , 31 , 32 , 33 ], MHC class I homologs (e.g., MICA [ 34 ]) and pMHC class I complexes [ 35 ].…”

Antigen recognition by human γδ T cells: one step closer to knowing

“…The clear implication of BTN2A1 in human Vγ9/Vδ2 T‐cell responses is a sort of homecoming for γδ T‐cell aficionados, because the related protein BTN3A1 had already been shown to be required for Vγ9/Vδ2 T‐cell responses to phosphoantigens 7 . Other butyrophilin family members with γδ T‐cell regulatory activity include BTNL3/BTNL8 (human Vγ4 + T cells), Btnl1/Btnl6 (mouse Vγ7 + T cells) and Skint1/Skint2 (mouse Vγ5 + T cells) 8 . Of note, HMB‐PP and IPP were previously shown to bind to the intracellular B30.2 domain of BTN3A1, 9 yet it has remained unclear whether and how this binding might translate to recognition of the extracellular portion of BTN3A1 via the Vγ9/Vδ2 T‐cell receptor (TCR).…”